Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury
Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysi...
Ausführliche Beschreibung
Autor*in: |
Manuel Flores Molina [verfasserIn] Mohamed N. Abdelnabi [verfasserIn] Sabrina Mazouz [verfasserIn] Deborah Villafranca-Baughman [verfasserIn] Vincent Quoc-Huy Trinh [verfasserIn] Shafi Muhammad [verfasserIn] Nathalie Bédard [verfasserIn] David Osorio Laverde [verfasserIn] Ghada S. Hassan [verfasserIn] Adriana Di Polo [verfasserIn] Naglaa H. Shoukry [verfasserIn] |
---|
Format: |
E-Artikel |
---|---|
Sprache: |
Englisch |
Erschienen: |
2022 |
---|
Schlagwörter: |
---|
Übergeordnetes Werk: |
In: Frontiers in Immunology - Frontiers Media S.A., 2011, 13(2022) |
---|---|
Übergeordnetes Werk: |
volume:13 ; year:2022 |
Links: |
---|
DOI / URN: |
10.3389/fimmu.2022.994480 |
---|
Katalog-ID: |
DOAJ022188606 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | DOAJ022188606 | ||
003 | DE-627 | ||
005 | 20230503004522.0 | ||
007 | cr uuu---uuuuu | ||
008 | 230226s2022 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.3389/fimmu.2022.994480 |2 doi | |
035 | |a (DE-627)DOAJ022188606 | ||
035 | |a (DE-599)DOAJ1a9adf263d8c472bbe8fcd4f23c43a10 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
050 | 0 | |a RC581-607 | |
100 | 0 | |a Manuel Flores Molina |e verfasserin |4 aut | |
245 | 1 | 0 | |a Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury |
264 | 1 | |c 2022 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a Computermedien |b c |2 rdamedia | ||
338 | |a Online-Ressource |b cr |2 rdacarrier | ||
520 | |a Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury. | ||
650 | 4 | |a liver | |
650 | 4 | |a macrophage | |
650 | 4 | |a acute injury | |
650 | 4 | |a CCl4 (carbon tetra chloride) | |
650 | 4 | |a Kupffer cell (KC) | |
650 | 4 | |a monocyte-derived macrophages | |
653 | 0 | |a Immunologic diseases. Allergy | |
700 | 0 | |a Manuel Flores Molina |e verfasserin |4 aut | |
700 | 0 | |a Mohamed N. Abdelnabi |e verfasserin |4 aut | |
700 | 0 | |a Mohamed N. Abdelnabi |e verfasserin |4 aut | |
700 | 0 | |a Sabrina Mazouz |e verfasserin |4 aut | |
700 | 0 | |a Sabrina Mazouz |e verfasserin |4 aut | |
700 | 0 | |a Deborah Villafranca-Baughman |e verfasserin |4 aut | |
700 | 0 | |a Deborah Villafranca-Baughman |e verfasserin |4 aut | |
700 | 0 | |a Vincent Quoc-Huy Trinh |e verfasserin |4 aut | |
700 | 0 | |a Shafi Muhammad |e verfasserin |4 aut | |
700 | 0 | |a Shafi Muhammad |e verfasserin |4 aut | |
700 | 0 | |a Nathalie Bédard |e verfasserin |4 aut | |
700 | 0 | |a David Osorio Laverde |e verfasserin |4 aut | |
700 | 0 | |a Ghada S. Hassan |e verfasserin |4 aut | |
700 | 0 | |a Adriana Di Polo |e verfasserin |4 aut | |
700 | 0 | |a Adriana Di Polo |e verfasserin |4 aut | |
700 | 0 | |a Naglaa H. Shoukry |e verfasserin |4 aut | |
700 | 0 | |a Naglaa H. Shoukry |e verfasserin |4 aut | |
773 | 0 | 8 | |i In |t Frontiers in Immunology |d Frontiers Media S.A., 2011 |g 13(2022) |w (DE-627)657998354 |w (DE-600)2606827-8 |x 16643224 |7 nnns |
773 | 1 | 8 | |g volume:13 |g year:2022 |
856 | 4 | 0 | |u https://doi.org/10.3389/fimmu.2022.994480 |z kostenfrei |
856 | 4 | 0 | |u https://doaj.org/article/1a9adf263d8c472bbe8fcd4f23c43a10 |z kostenfrei |
856 | 4 | 0 | |u https://www.frontiersin.org/articles/10.3389/fimmu.2022.994480/full |z kostenfrei |
856 | 4 | 2 | |u https://doaj.org/toc/1664-3224 |y Journal toc |z kostenfrei |
912 | |a GBV_USEFLAG_A | ||
912 | |a SYSFLAG_A | ||
912 | |a GBV_DOAJ | ||
912 | |a SSG-OLC-PHA | ||
912 | |a GBV_ILN_11 | ||
912 | |a GBV_ILN_20 | ||
912 | |a GBV_ILN_22 | ||
912 | |a GBV_ILN_23 | ||
912 | |a GBV_ILN_24 | ||
912 | |a GBV_ILN_39 | ||
912 | |a GBV_ILN_40 | ||
912 | |a GBV_ILN_60 | ||
912 | |a GBV_ILN_62 | ||
912 | |a GBV_ILN_63 | ||
912 | |a GBV_ILN_65 | ||
912 | |a GBV_ILN_69 | ||
912 | |a GBV_ILN_73 | ||
912 | |a GBV_ILN_74 | ||
912 | |a GBV_ILN_95 | ||
912 | |a GBV_ILN_105 | ||
912 | |a GBV_ILN_110 | ||
912 | |a GBV_ILN_151 | ||
912 | |a GBV_ILN_161 | ||
912 | |a GBV_ILN_170 | ||
912 | |a GBV_ILN_206 | ||
912 | |a GBV_ILN_213 | ||
912 | |a GBV_ILN_230 | ||
912 | |a GBV_ILN_285 | ||
912 | |a GBV_ILN_293 | ||
912 | |a GBV_ILN_602 | ||
912 | |a GBV_ILN_2003 | ||
912 | |a GBV_ILN_2014 | ||
912 | |a GBV_ILN_4012 | ||
912 | |a GBV_ILN_4037 | ||
912 | |a GBV_ILN_4112 | ||
912 | |a GBV_ILN_4125 | ||
912 | |a GBV_ILN_4126 | ||
912 | |a GBV_ILN_4249 | ||
912 | |a GBV_ILN_4305 | ||
912 | |a GBV_ILN_4306 | ||
912 | |a GBV_ILN_4307 | ||
912 | |a GBV_ILN_4313 | ||
912 | |a GBV_ILN_4322 | ||
912 | |a GBV_ILN_4323 | ||
912 | |a GBV_ILN_4324 | ||
912 | |a GBV_ILN_4325 | ||
912 | |a GBV_ILN_4338 | ||
912 | |a GBV_ILN_4367 | ||
912 | |a GBV_ILN_4700 | ||
951 | |a AR | ||
952 | |d 13 |j 2022 |
author_variant |
m f m mfm m f m mfm m n a mna m n a mna s m sm s m sm d v b dvb d v b dvb v q h t vqht s m sm s m sm n b nb d o l dol g s h gsh a d p adp a d p adp n h s nhs n h s nhs |
---|---|
matchkey_str |
article:16643224:2022----::itntptadsrbtoadoeokpfreladooyeeiemcoh |
hierarchy_sort_str |
2022 |
callnumber-subject-code |
RC |
publishDate |
2022 |
allfields |
10.3389/fimmu.2022.994480 doi (DE-627)DOAJ022188606 (DE-599)DOAJ1a9adf263d8c472bbe8fcd4f23c43a10 DE-627 ger DE-627 rakwb eng RC581-607 Manuel Flores Molina verfasserin aut Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury. liver macrophage acute injury CCl4 (carbon tetra chloride) Kupffer cell (KC) monocyte-derived macrophages Immunologic diseases. Allergy Manuel Flores Molina verfasserin aut Mohamed N. Abdelnabi verfasserin aut Mohamed N. Abdelnabi verfasserin aut Sabrina Mazouz verfasserin aut Sabrina Mazouz verfasserin aut Deborah Villafranca-Baughman verfasserin aut Deborah Villafranca-Baughman verfasserin aut Vincent Quoc-Huy Trinh verfasserin aut Shafi Muhammad verfasserin aut Shafi Muhammad verfasserin aut Nathalie Bédard verfasserin aut David Osorio Laverde verfasserin aut Ghada S. Hassan verfasserin aut Adriana Di Polo verfasserin aut Adriana Di Polo verfasserin aut Naglaa H. Shoukry verfasserin aut Naglaa H. Shoukry verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.994480 kostenfrei https://doaj.org/article/1a9adf263d8c472bbe8fcd4f23c43a10 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.994480/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022 |
spelling |
10.3389/fimmu.2022.994480 doi (DE-627)DOAJ022188606 (DE-599)DOAJ1a9adf263d8c472bbe8fcd4f23c43a10 DE-627 ger DE-627 rakwb eng RC581-607 Manuel Flores Molina verfasserin aut Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury. liver macrophage acute injury CCl4 (carbon tetra chloride) Kupffer cell (KC) monocyte-derived macrophages Immunologic diseases. Allergy Manuel Flores Molina verfasserin aut Mohamed N. Abdelnabi verfasserin aut Mohamed N. Abdelnabi verfasserin aut Sabrina Mazouz verfasserin aut Sabrina Mazouz verfasserin aut Deborah Villafranca-Baughman verfasserin aut Deborah Villafranca-Baughman verfasserin aut Vincent Quoc-Huy Trinh verfasserin aut Shafi Muhammad verfasserin aut Shafi Muhammad verfasserin aut Nathalie Bédard verfasserin aut David Osorio Laverde verfasserin aut Ghada S. Hassan verfasserin aut Adriana Di Polo verfasserin aut Adriana Di Polo verfasserin aut Naglaa H. Shoukry verfasserin aut Naglaa H. Shoukry verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.994480 kostenfrei https://doaj.org/article/1a9adf263d8c472bbe8fcd4f23c43a10 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.994480/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022 |
allfields_unstemmed |
10.3389/fimmu.2022.994480 doi (DE-627)DOAJ022188606 (DE-599)DOAJ1a9adf263d8c472bbe8fcd4f23c43a10 DE-627 ger DE-627 rakwb eng RC581-607 Manuel Flores Molina verfasserin aut Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury. liver macrophage acute injury CCl4 (carbon tetra chloride) Kupffer cell (KC) monocyte-derived macrophages Immunologic diseases. Allergy Manuel Flores Molina verfasserin aut Mohamed N. Abdelnabi verfasserin aut Mohamed N. Abdelnabi verfasserin aut Sabrina Mazouz verfasserin aut Sabrina Mazouz verfasserin aut Deborah Villafranca-Baughman verfasserin aut Deborah Villafranca-Baughman verfasserin aut Vincent Quoc-Huy Trinh verfasserin aut Shafi Muhammad verfasserin aut Shafi Muhammad verfasserin aut Nathalie Bédard verfasserin aut David Osorio Laverde verfasserin aut Ghada S. Hassan verfasserin aut Adriana Di Polo verfasserin aut Adriana Di Polo verfasserin aut Naglaa H. Shoukry verfasserin aut Naglaa H. Shoukry verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.994480 kostenfrei https://doaj.org/article/1a9adf263d8c472bbe8fcd4f23c43a10 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.994480/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022 |
allfieldsGer |
10.3389/fimmu.2022.994480 doi (DE-627)DOAJ022188606 (DE-599)DOAJ1a9adf263d8c472bbe8fcd4f23c43a10 DE-627 ger DE-627 rakwb eng RC581-607 Manuel Flores Molina verfasserin aut Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury. liver macrophage acute injury CCl4 (carbon tetra chloride) Kupffer cell (KC) monocyte-derived macrophages Immunologic diseases. Allergy Manuel Flores Molina verfasserin aut Mohamed N. Abdelnabi verfasserin aut Mohamed N. Abdelnabi verfasserin aut Sabrina Mazouz verfasserin aut Sabrina Mazouz verfasserin aut Deborah Villafranca-Baughman verfasserin aut Deborah Villafranca-Baughman verfasserin aut Vincent Quoc-Huy Trinh verfasserin aut Shafi Muhammad verfasserin aut Shafi Muhammad verfasserin aut Nathalie Bédard verfasserin aut David Osorio Laverde verfasserin aut Ghada S. Hassan verfasserin aut Adriana Di Polo verfasserin aut Adriana Di Polo verfasserin aut Naglaa H. Shoukry verfasserin aut Naglaa H. Shoukry verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.994480 kostenfrei https://doaj.org/article/1a9adf263d8c472bbe8fcd4f23c43a10 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.994480/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022 |
allfieldsSound |
10.3389/fimmu.2022.994480 doi (DE-627)DOAJ022188606 (DE-599)DOAJ1a9adf263d8c472bbe8fcd4f23c43a10 DE-627 ger DE-627 rakwb eng RC581-607 Manuel Flores Molina verfasserin aut Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury. liver macrophage acute injury CCl4 (carbon tetra chloride) Kupffer cell (KC) monocyte-derived macrophages Immunologic diseases. Allergy Manuel Flores Molina verfasserin aut Mohamed N. Abdelnabi verfasserin aut Mohamed N. Abdelnabi verfasserin aut Sabrina Mazouz verfasserin aut Sabrina Mazouz verfasserin aut Deborah Villafranca-Baughman verfasserin aut Deborah Villafranca-Baughman verfasserin aut Vincent Quoc-Huy Trinh verfasserin aut Shafi Muhammad verfasserin aut Shafi Muhammad verfasserin aut Nathalie Bédard verfasserin aut David Osorio Laverde verfasserin aut Ghada S. Hassan verfasserin aut Adriana Di Polo verfasserin aut Adriana Di Polo verfasserin aut Naglaa H. Shoukry verfasserin aut Naglaa H. Shoukry verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.994480 kostenfrei https://doaj.org/article/1a9adf263d8c472bbe8fcd4f23c43a10 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.994480/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022 |
language |
English |
source |
In Frontiers in Immunology 13(2022) volume:13 year:2022 |
sourceStr |
In Frontiers in Immunology 13(2022) volume:13 year:2022 |
format_phy_str_mv |
Article |
institution |
findex.gbv.de |
topic_facet |
liver macrophage acute injury CCl4 (carbon tetra chloride) Kupffer cell (KC) monocyte-derived macrophages Immunologic diseases. Allergy |
isfreeaccess_bool |
true |
container_title |
Frontiers in Immunology |
authorswithroles_txt_mv |
Manuel Flores Molina @@aut@@ Mohamed N. Abdelnabi @@aut@@ Sabrina Mazouz @@aut@@ Deborah Villafranca-Baughman @@aut@@ Vincent Quoc-Huy Trinh @@aut@@ Shafi Muhammad @@aut@@ Nathalie Bédard @@aut@@ David Osorio Laverde @@aut@@ Ghada S. Hassan @@aut@@ Adriana Di Polo @@aut@@ Naglaa H. Shoukry @@aut@@ |
publishDateDaySort_date |
2022-01-01T00:00:00Z |
hierarchy_top_id |
657998354 |
id |
DOAJ022188606 |
language_de |
englisch |
fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ022188606</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230503004522.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230226s2022 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.3389/fimmu.2022.994480</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ022188606</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ1a9adf263d8c472bbe8fcd4f23c43a10</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC581-607</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Manuel Flores Molina</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2022</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">liver</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">macrophage</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">acute injury</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">CCl4 (carbon tetra chloride)</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Kupffer cell (KC)</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">monocyte-derived macrophages</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Immunologic diseases. Allergy</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Manuel Flores Molina</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mohamed N. Abdelnabi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mohamed N. Abdelnabi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sabrina Mazouz</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sabrina Mazouz</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Deborah Villafranca-Baughman</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Deborah Villafranca-Baughman</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Vincent Quoc-Huy Trinh</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Shafi Muhammad</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Shafi Muhammad</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nathalie Bédard</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">David Osorio Laverde</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ghada S. Hassan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Adriana Di Polo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Adriana Di Polo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Naglaa H. Shoukry</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Naglaa H. Shoukry</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Frontiers in Immunology</subfield><subfield code="d">Frontiers Media S.A., 2011</subfield><subfield code="g">13(2022)</subfield><subfield code="w">(DE-627)657998354</subfield><subfield code="w">(DE-600)2606827-8</subfield><subfield code="x">16643224</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:13</subfield><subfield code="g">year:2022</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.3389/fimmu.2022.994480</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/1a9adf263d8c472bbe8fcd4f23c43a10</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://www.frontiersin.org/articles/10.3389/fimmu.2022.994480/full</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/1664-3224</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">13</subfield><subfield code="j">2022</subfield></datafield></record></collection>
|
callnumber-first |
R - Medicine |
author |
Manuel Flores Molina |
spellingShingle |
Manuel Flores Molina misc RC581-607 misc liver misc macrophage misc acute injury misc CCl4 (carbon tetra chloride) misc Kupffer cell (KC) misc monocyte-derived macrophages misc Immunologic diseases. Allergy Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury |
authorStr |
Manuel Flores Molina |
ppnlink_with_tag_str_mv |
@@773@@(DE-627)657998354 |
format |
electronic Article |
delete_txt_mv |
keep |
author_role |
aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut |
collection |
DOAJ |
remote_str |
true |
callnumber-label |
RC581-607 |
illustrated |
Not Illustrated |
issn |
16643224 |
topic_title |
RC581-607 Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury liver macrophage acute injury CCl4 (carbon tetra chloride) Kupffer cell (KC) monocyte-derived macrophages |
topic |
misc RC581-607 misc liver misc macrophage misc acute injury misc CCl4 (carbon tetra chloride) misc Kupffer cell (KC) misc monocyte-derived macrophages misc Immunologic diseases. Allergy |
topic_unstemmed |
misc RC581-607 misc liver misc macrophage misc acute injury misc CCl4 (carbon tetra chloride) misc Kupffer cell (KC) misc monocyte-derived macrophages misc Immunologic diseases. Allergy |
topic_browse |
misc RC581-607 misc liver misc macrophage misc acute injury misc CCl4 (carbon tetra chloride) misc Kupffer cell (KC) misc monocyte-derived macrophages misc Immunologic diseases. Allergy |
format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
format_main_str_mv |
Text Zeitschrift/Artikel |
carriertype_str_mv |
cr |
hierarchy_parent_title |
Frontiers in Immunology |
hierarchy_parent_id |
657998354 |
hierarchy_top_title |
Frontiers in Immunology |
isfreeaccess_txt |
true |
familylinks_str_mv |
(DE-627)657998354 (DE-600)2606827-8 |
title |
Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury |
ctrlnum |
(DE-627)DOAJ022188606 (DE-599)DOAJ1a9adf263d8c472bbe8fcd4f23c43a10 |
title_full |
Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury |
author_sort |
Manuel Flores Molina |
journal |
Frontiers in Immunology |
journalStr |
Frontiers in Immunology |
callnumber-first-code |
R |
lang_code |
eng |
isOA_bool |
true |
recordtype |
marc |
publishDateSort |
2022 |
contenttype_str_mv |
txt |
author_browse |
Manuel Flores Molina Mohamed N. Abdelnabi Sabrina Mazouz Deborah Villafranca-Baughman Vincent Quoc-Huy Trinh Shafi Muhammad Nathalie Bédard David Osorio Laverde Ghada S. Hassan Adriana Di Polo Naglaa H. Shoukry |
container_volume |
13 |
class |
RC581-607 |
format_se |
Elektronische Aufsätze |
author-letter |
Manuel Flores Molina |
doi_str_mv |
10.3389/fimmu.2022.994480 |
author2-role |
verfasserin |
title_sort |
distinct spatial distribution and roles of kupffer cells and monocyte-derived macrophages in mouse acute liver injury |
callnumber |
RC581-607 |
title_auth |
Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury |
abstract |
Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury. |
abstractGer |
Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury. |
abstract_unstemmed |
Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury. |
collection_details |
GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 |
title_short |
Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury |
url |
https://doi.org/10.3389/fimmu.2022.994480 https://doaj.org/article/1a9adf263d8c472bbe8fcd4f23c43a10 https://www.frontiersin.org/articles/10.3389/fimmu.2022.994480/full https://doaj.org/toc/1664-3224 |
remote_bool |
true |
author2 |
Manuel Flores Molina Mohamed N. Abdelnabi Sabrina Mazouz Deborah Villafranca-Baughman Vincent Quoc-Huy Trinh Shafi Muhammad Nathalie Bédard David Osorio Laverde Ghada S. Hassan Adriana Di Polo Naglaa H. Shoukry |
author2Str |
Manuel Flores Molina Mohamed N. Abdelnabi Sabrina Mazouz Deborah Villafranca-Baughman Vincent Quoc-Huy Trinh Shafi Muhammad Nathalie Bédard David Osorio Laverde Ghada S. Hassan Adriana Di Polo Naglaa H. Shoukry |
ppnlink |
657998354 |
callnumber-subject |
RC - Internal Medicine |
mediatype_str_mv |
c |
isOA_txt |
true |
hochschulschrift_bool |
false |
doi_str |
10.3389/fimmu.2022.994480 |
callnumber-a |
RC581-607 |
up_date |
2024-07-04T00:34:30.234Z |
_version_ |
1803606577895178240 |
fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ022188606</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230503004522.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230226s2022 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.3389/fimmu.2022.994480</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ022188606</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ1a9adf263d8c472bbe8fcd4f23c43a10</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC581-607</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Manuel Flores Molina</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2022</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">liver</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">macrophage</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">acute injury</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">CCl4 (carbon tetra chloride)</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Kupffer cell (KC)</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">monocyte-derived macrophages</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Immunologic diseases. Allergy</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Manuel Flores Molina</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mohamed N. Abdelnabi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mohamed N. Abdelnabi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sabrina Mazouz</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sabrina Mazouz</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Deborah Villafranca-Baughman</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Deborah Villafranca-Baughman</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Vincent Quoc-Huy Trinh</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Shafi Muhammad</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Shafi Muhammad</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nathalie Bédard</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">David Osorio Laverde</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ghada S. Hassan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Adriana Di Polo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Adriana Di Polo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Naglaa H. Shoukry</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Naglaa H. Shoukry</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Frontiers in Immunology</subfield><subfield code="d">Frontiers Media S.A., 2011</subfield><subfield code="g">13(2022)</subfield><subfield code="w">(DE-627)657998354</subfield><subfield code="w">(DE-600)2606827-8</subfield><subfield code="x">16643224</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:13</subfield><subfield code="g">year:2022</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.3389/fimmu.2022.994480</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/1a9adf263d8c472bbe8fcd4f23c43a10</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://www.frontiersin.org/articles/10.3389/fimmu.2022.994480/full</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/1664-3224</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">13</subfield><subfield code="j">2022</subfield></datafield></record></collection>
|
score |
7.399823 |