Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite
Background Previous sheep models of asthma are based on sheep sensitized to nematode (Ascaris) allergens and these have been used to evaluate the physiological and pharmacological effects of potential anti-asthma agents. The immunological mechanisms associated with the allergic response in sheep lun...
Ausführliche Beschreibung
Autor*in: |
Bischof, R. J. [verfasserIn] Snibson, K. [verfasserIn] Shaw, R. [verfasserIn] |
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Oxford, UK: Blackwell Science Ltd ; 2003 |
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Online-Ressource |
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2003 ; Blackwell Publishing Journal Backfiles 1879-2005 |
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Übergeordnetes Werk: |
In: Clinical & experimental allergy - Oxford : Blackwell Science, 1989, 33(2003), 3, Seite 0 |
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volume:33 ; year:2003 ; number:3 ; pages:0 |
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DOI / URN: |
10.1046/j.1365-2222.2003.01534.x |
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NLEJ242607888 |
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245 | 1 | 0 | |a Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite |
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520 | |a Background Previous sheep models of asthma are based on sheep sensitized to nematode (Ascaris) allergens and these have been used to evaluate the physiological and pharmacological effects of potential anti-asthma agents. The immunological mechanisms associated with the allergic response in sheep lungs has not been examined in detail.Objective To develop an experimental sheep model of allergic lung inflammation based on a relevant major human allergen, house dust mite, and to define the immunological features of the allergic response in this model.Methods Sheep immunized subcutaneously with solubilized house dust mite extract were given a single bronchial challenge with house dust mite. Bronchoalveolar lavage (BAL) and peripheral blood leucocytes were collected before and after challenge for flow cytometry, and tissue samples were taken post-mortem (48 h post-challenge) for histology and immunohistochemical analyses.Results Immunizations with 50 μg house dust mite induced an allergen-specific IgE response in 50 to 60% of sheep (allergic sheep), with higher antigen doses increasing specific IgG1 but not IgE. Lung challenge of allergic sheep with house dust mite led to the initial recruitment of neutrophils (at 6 h post-challenge) followed by eosinophils and activated lymphocytes into the lung tissue and BAL, similar to the late-phase allergic response seen in human asthma. Eosinophil recruitment peaked at 48 h post-challenge, representing 10 to 33% of BAL leucocytes in allergen-challenged allergic sheep compared to 0 to 3% in allergen-challenged control (naïve) sheep. Lymphocytes recovered from the lung after allergen challenge were enriched for CD4+ T cells and were more activated than lymphocytes in blood. There was significant down-regulation of CD62L (L-selectin) and CD49d (VLA-4) expression after allergen challenge on BAL eosinophils and lymphocytes compared to blood. In addition, VCAM-1 (ligand for VLA-4) was up-regulated on blood vessels of allergen-challenged lungs. Eosinophils, CD4+ T cells and CD45R+ B cells were the most prominent leucocytes found in lung tissue 48 h after allergen challenge.Conclusion This study demonstrates, for the first time, the ability of house dust mite to induce allergic responses in sheep lungs. This novel sheep model of allergic lung inflammation using relevant human allergens, exhibits similarities to human asthmatic disease and will be a useful tool for studies of the immunological and physiological mechanisms of allergic asthma. | ||
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650 | 4 | |a allergic lung inflammation | |
700 | 1 | |a Snibson, K. |e verfasserin |4 aut | |
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700 | 1 | |a Meeusen, E. N. T |4 oth | |
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10.1046/j.1365-2222.2003.01534.x doi (DE-627)NLEJ242607888 DE-627 ger DE-627 rakwb Bischof, R. J. verfasserin aut Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite Oxford, UK Blackwell Science Ltd 2003 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Background Previous sheep models of asthma are based on sheep sensitized to nematode (Ascaris) allergens and these have been used to evaluate the physiological and pharmacological effects of potential anti-asthma agents. The immunological mechanisms associated with the allergic response in sheep lungs has not been examined in detail.Objective To develop an experimental sheep model of allergic lung inflammation based on a relevant major human allergen, house dust mite, and to define the immunological features of the allergic response in this model.Methods Sheep immunized subcutaneously with solubilized house dust mite extract were given a single bronchial challenge with house dust mite. Bronchoalveolar lavage (BAL) and peripheral blood leucocytes were collected before and after challenge for flow cytometry, and tissue samples were taken post-mortem (48 h post-challenge) for histology and immunohistochemical analyses.Results Immunizations with 50 μg house dust mite induced an allergen-specific IgE response in 50 to 60% of sheep (allergic sheep), with higher antigen doses increasing specific IgG1 but not IgE. Lung challenge of allergic sheep with house dust mite led to the initial recruitment of neutrophils (at 6 h post-challenge) followed by eosinophils and activated lymphocytes into the lung tissue and BAL, similar to the late-phase allergic response seen in human asthma. Eosinophil recruitment peaked at 48 h post-challenge, representing 10 to 33% of BAL leucocytes in allergen-challenged allergic sheep compared to 0 to 3% in allergen-challenged control (naïve) sheep. Lymphocytes recovered from the lung after allergen challenge were enriched for CD4+ T cells and were more activated than lymphocytes in blood. There was significant down-regulation of CD62L (L-selectin) and CD49d (VLA-4) expression after allergen challenge on BAL eosinophils and lymphocytes compared to blood. In addition, VCAM-1 (ligand for VLA-4) was up-regulated on blood vessels of allergen-challenged lungs. Eosinophils, CD4+ T cells and CD45R+ B cells were the most prominent leucocytes found in lung tissue 48 h after allergen challenge.Conclusion This study demonstrates, for the first time, the ability of house dust mite to induce allergic responses in sheep lungs. This novel sheep model of allergic lung inflammation using relevant human allergens, exhibits similarities to human asthmatic disease and will be a useful tool for studies of the immunological and physiological mechanisms of allergic asthma. 2003 Blackwell Publishing Journal Backfiles 1879-2005 |2003|||||||||| allergic lung inflammation Snibson, K. verfasserin aut Shaw, R. verfasserin aut Meeusen, E. N. T oth In Clinical & experimental allergy Oxford : Blackwell Science, 1989 33(2003), 3, Seite 0 Online-Ressource (DE-627)NLEJ243926391 (DE-600)2004469-0 1365-2222 nnns volume:33 year:2003 number:3 pages:0 http://dx.doi.org/10.1046/j.1365-2222.2003.01534.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 33 2003 3 0 |
spelling |
10.1046/j.1365-2222.2003.01534.x doi (DE-627)NLEJ242607888 DE-627 ger DE-627 rakwb Bischof, R. J. verfasserin aut Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite Oxford, UK Blackwell Science Ltd 2003 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Background Previous sheep models of asthma are based on sheep sensitized to nematode (Ascaris) allergens and these have been used to evaluate the physiological and pharmacological effects of potential anti-asthma agents. The immunological mechanisms associated with the allergic response in sheep lungs has not been examined in detail.Objective To develop an experimental sheep model of allergic lung inflammation based on a relevant major human allergen, house dust mite, and to define the immunological features of the allergic response in this model.Methods Sheep immunized subcutaneously with solubilized house dust mite extract were given a single bronchial challenge with house dust mite. Bronchoalveolar lavage (BAL) and peripheral blood leucocytes were collected before and after challenge for flow cytometry, and tissue samples were taken post-mortem (48 h post-challenge) for histology and immunohistochemical analyses.Results Immunizations with 50 μg house dust mite induced an allergen-specific IgE response in 50 to 60% of sheep (allergic sheep), with higher antigen doses increasing specific IgG1 but not IgE. Lung challenge of allergic sheep with house dust mite led to the initial recruitment of neutrophils (at 6 h post-challenge) followed by eosinophils and activated lymphocytes into the lung tissue and BAL, similar to the late-phase allergic response seen in human asthma. Eosinophil recruitment peaked at 48 h post-challenge, representing 10 to 33% of BAL leucocytes in allergen-challenged allergic sheep compared to 0 to 3% in allergen-challenged control (naïve) sheep. Lymphocytes recovered from the lung after allergen challenge were enriched for CD4+ T cells and were more activated than lymphocytes in blood. There was significant down-regulation of CD62L (L-selectin) and CD49d (VLA-4) expression after allergen challenge on BAL eosinophils and lymphocytes compared to blood. In addition, VCAM-1 (ligand for VLA-4) was up-regulated on blood vessels of allergen-challenged lungs. Eosinophils, CD4+ T cells and CD45R+ B cells were the most prominent leucocytes found in lung tissue 48 h after allergen challenge.Conclusion This study demonstrates, for the first time, the ability of house dust mite to induce allergic responses in sheep lungs. This novel sheep model of allergic lung inflammation using relevant human allergens, exhibits similarities to human asthmatic disease and will be a useful tool for studies of the immunological and physiological mechanisms of allergic asthma. 2003 Blackwell Publishing Journal Backfiles 1879-2005 |2003|||||||||| allergic lung inflammation Snibson, K. verfasserin aut Shaw, R. verfasserin aut Meeusen, E. N. T oth In Clinical & experimental allergy Oxford : Blackwell Science, 1989 33(2003), 3, Seite 0 Online-Ressource (DE-627)NLEJ243926391 (DE-600)2004469-0 1365-2222 nnns volume:33 year:2003 number:3 pages:0 http://dx.doi.org/10.1046/j.1365-2222.2003.01534.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 33 2003 3 0 |
allfields_unstemmed |
10.1046/j.1365-2222.2003.01534.x doi (DE-627)NLEJ242607888 DE-627 ger DE-627 rakwb Bischof, R. J. verfasserin aut Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite Oxford, UK Blackwell Science Ltd 2003 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Background Previous sheep models of asthma are based on sheep sensitized to nematode (Ascaris) allergens and these have been used to evaluate the physiological and pharmacological effects of potential anti-asthma agents. The immunological mechanisms associated with the allergic response in sheep lungs has not been examined in detail.Objective To develop an experimental sheep model of allergic lung inflammation based on a relevant major human allergen, house dust mite, and to define the immunological features of the allergic response in this model.Methods Sheep immunized subcutaneously with solubilized house dust mite extract were given a single bronchial challenge with house dust mite. Bronchoalveolar lavage (BAL) and peripheral blood leucocytes were collected before and after challenge for flow cytometry, and tissue samples were taken post-mortem (48 h post-challenge) for histology and immunohistochemical analyses.Results Immunizations with 50 μg house dust mite induced an allergen-specific IgE response in 50 to 60% of sheep (allergic sheep), with higher antigen doses increasing specific IgG1 but not IgE. Lung challenge of allergic sheep with house dust mite led to the initial recruitment of neutrophils (at 6 h post-challenge) followed by eosinophils and activated lymphocytes into the lung tissue and BAL, similar to the late-phase allergic response seen in human asthma. Eosinophil recruitment peaked at 48 h post-challenge, representing 10 to 33% of BAL leucocytes in allergen-challenged allergic sheep compared to 0 to 3% in allergen-challenged control (naïve) sheep. Lymphocytes recovered from the lung after allergen challenge were enriched for CD4+ T cells and were more activated than lymphocytes in blood. There was significant down-regulation of CD62L (L-selectin) and CD49d (VLA-4) expression after allergen challenge on BAL eosinophils and lymphocytes compared to blood. In addition, VCAM-1 (ligand for VLA-4) was up-regulated on blood vessels of allergen-challenged lungs. Eosinophils, CD4+ T cells and CD45R+ B cells were the most prominent leucocytes found in lung tissue 48 h after allergen challenge.Conclusion This study demonstrates, for the first time, the ability of house dust mite to induce allergic responses in sheep lungs. This novel sheep model of allergic lung inflammation using relevant human allergens, exhibits similarities to human asthmatic disease and will be a useful tool for studies of the immunological and physiological mechanisms of allergic asthma. 2003 Blackwell Publishing Journal Backfiles 1879-2005 |2003|||||||||| allergic lung inflammation Snibson, K. verfasserin aut Shaw, R. verfasserin aut Meeusen, E. N. T oth In Clinical & experimental allergy Oxford : Blackwell Science, 1989 33(2003), 3, Seite 0 Online-Ressource (DE-627)NLEJ243926391 (DE-600)2004469-0 1365-2222 nnns volume:33 year:2003 number:3 pages:0 http://dx.doi.org/10.1046/j.1365-2222.2003.01534.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 33 2003 3 0 |
allfieldsGer |
10.1046/j.1365-2222.2003.01534.x doi (DE-627)NLEJ242607888 DE-627 ger DE-627 rakwb Bischof, R. J. verfasserin aut Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite Oxford, UK Blackwell Science Ltd 2003 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Background Previous sheep models of asthma are based on sheep sensitized to nematode (Ascaris) allergens and these have been used to evaluate the physiological and pharmacological effects of potential anti-asthma agents. The immunological mechanisms associated with the allergic response in sheep lungs has not been examined in detail.Objective To develop an experimental sheep model of allergic lung inflammation based on a relevant major human allergen, house dust mite, and to define the immunological features of the allergic response in this model.Methods Sheep immunized subcutaneously with solubilized house dust mite extract were given a single bronchial challenge with house dust mite. Bronchoalveolar lavage (BAL) and peripheral blood leucocytes were collected before and after challenge for flow cytometry, and tissue samples were taken post-mortem (48 h post-challenge) for histology and immunohistochemical analyses.Results Immunizations with 50 μg house dust mite induced an allergen-specific IgE response in 50 to 60% of sheep (allergic sheep), with higher antigen doses increasing specific IgG1 but not IgE. Lung challenge of allergic sheep with house dust mite led to the initial recruitment of neutrophils (at 6 h post-challenge) followed by eosinophils and activated lymphocytes into the lung tissue and BAL, similar to the late-phase allergic response seen in human asthma. Eosinophil recruitment peaked at 48 h post-challenge, representing 10 to 33% of BAL leucocytes in allergen-challenged allergic sheep compared to 0 to 3% in allergen-challenged control (naïve) sheep. Lymphocytes recovered from the lung after allergen challenge were enriched for CD4+ T cells and were more activated than lymphocytes in blood. There was significant down-regulation of CD62L (L-selectin) and CD49d (VLA-4) expression after allergen challenge on BAL eosinophils and lymphocytes compared to blood. In addition, VCAM-1 (ligand for VLA-4) was up-regulated on blood vessels of allergen-challenged lungs. Eosinophils, CD4+ T cells and CD45R+ B cells were the most prominent leucocytes found in lung tissue 48 h after allergen challenge.Conclusion This study demonstrates, for the first time, the ability of house dust mite to induce allergic responses in sheep lungs. This novel sheep model of allergic lung inflammation using relevant human allergens, exhibits similarities to human asthmatic disease and will be a useful tool for studies of the immunological and physiological mechanisms of allergic asthma. 2003 Blackwell Publishing Journal Backfiles 1879-2005 |2003|||||||||| allergic lung inflammation Snibson, K. verfasserin aut Shaw, R. verfasserin aut Meeusen, E. N. T oth In Clinical & experimental allergy Oxford : Blackwell Science, 1989 33(2003), 3, Seite 0 Online-Ressource (DE-627)NLEJ243926391 (DE-600)2004469-0 1365-2222 nnns volume:33 year:2003 number:3 pages:0 http://dx.doi.org/10.1046/j.1365-2222.2003.01534.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 33 2003 3 0 |
allfieldsSound |
10.1046/j.1365-2222.2003.01534.x doi (DE-627)NLEJ242607888 DE-627 ger DE-627 rakwb Bischof, R. J. verfasserin aut Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite Oxford, UK Blackwell Science Ltd 2003 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Background Previous sheep models of asthma are based on sheep sensitized to nematode (Ascaris) allergens and these have been used to evaluate the physiological and pharmacological effects of potential anti-asthma agents. The immunological mechanisms associated with the allergic response in sheep lungs has not been examined in detail.Objective To develop an experimental sheep model of allergic lung inflammation based on a relevant major human allergen, house dust mite, and to define the immunological features of the allergic response in this model.Methods Sheep immunized subcutaneously with solubilized house dust mite extract were given a single bronchial challenge with house dust mite. Bronchoalveolar lavage (BAL) and peripheral blood leucocytes were collected before and after challenge for flow cytometry, and tissue samples were taken post-mortem (48 h post-challenge) for histology and immunohistochemical analyses.Results Immunizations with 50 μg house dust mite induced an allergen-specific IgE response in 50 to 60% of sheep (allergic sheep), with higher antigen doses increasing specific IgG1 but not IgE. Lung challenge of allergic sheep with house dust mite led to the initial recruitment of neutrophils (at 6 h post-challenge) followed by eosinophils and activated lymphocytes into the lung tissue and BAL, similar to the late-phase allergic response seen in human asthma. Eosinophil recruitment peaked at 48 h post-challenge, representing 10 to 33% of BAL leucocytes in allergen-challenged allergic sheep compared to 0 to 3% in allergen-challenged control (naïve) sheep. Lymphocytes recovered from the lung after allergen challenge were enriched for CD4+ T cells and were more activated than lymphocytes in blood. There was significant down-regulation of CD62L (L-selectin) and CD49d (VLA-4) expression after allergen challenge on BAL eosinophils and lymphocytes compared to blood. In addition, VCAM-1 (ligand for VLA-4) was up-regulated on blood vessels of allergen-challenged lungs. Eosinophils, CD4+ T cells and CD45R+ B cells were the most prominent leucocytes found in lung tissue 48 h after allergen challenge.Conclusion This study demonstrates, for the first time, the ability of house dust mite to induce allergic responses in sheep lungs. This novel sheep model of allergic lung inflammation using relevant human allergens, exhibits similarities to human asthmatic disease and will be a useful tool for studies of the immunological and physiological mechanisms of allergic asthma. 2003 Blackwell Publishing Journal Backfiles 1879-2005 |2003|||||||||| allergic lung inflammation Snibson, K. verfasserin aut Shaw, R. verfasserin aut Meeusen, E. N. T oth In Clinical & experimental allergy Oxford : Blackwell Science, 1989 33(2003), 3, Seite 0 Online-Ressource (DE-627)NLEJ243926391 (DE-600)2004469-0 1365-2222 nnns volume:33 year:2003 number:3 pages:0 http://dx.doi.org/10.1046/j.1365-2222.2003.01534.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 33 2003 3 0 |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">NLEJ242607888</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230506095102.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">120427s2003 xx |||||o 00| ||und c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1046/j.1365-2222.2003.01534.x</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)NLEJ242607888</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="100" ind1="1" ind2=" "><subfield code="a">Bischof, R. J.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">Oxford, UK</subfield><subfield code="b">Blackwell Science Ltd</subfield><subfield code="c">2003</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">z</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zu</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background Previous sheep models of asthma are based on sheep sensitized to nematode (Ascaris) allergens and these have been used to evaluate the physiological and pharmacological effects of potential anti-asthma agents. The immunological mechanisms associated with the allergic response in sheep lungs has not been examined in detail.Objective To develop an experimental sheep model of allergic lung inflammation based on a relevant major human allergen, house dust mite, and to define the immunological features of the allergic response in this model.Methods Sheep immunized subcutaneously with solubilized house dust mite extract were given a single bronchial challenge with house dust mite. Bronchoalveolar lavage (BAL) and peripheral blood leucocytes were collected before and after challenge for flow cytometry, and tissue samples were taken post-mortem (48 h post-challenge) for histology and immunohistochemical analyses.Results Immunizations with 50 μg house dust mite induced an allergen-specific IgE response in 50 to 60% of sheep (allergic sheep), with higher antigen doses increasing specific IgG1 but not IgE. Lung challenge of allergic sheep with house dust mite led to the initial recruitment of neutrophils (at 6 h post-challenge) followed by eosinophils and activated lymphocytes into the lung tissue and BAL, similar to the late-phase allergic response seen in human asthma. Eosinophil recruitment peaked at 48 h post-challenge, representing 10 to 33% of BAL leucocytes in allergen-challenged allergic sheep compared to 0 to 3% in allergen-challenged control (naïve) sheep. Lymphocytes recovered from the lung after allergen challenge were enriched for CD4+ T cells and were more activated than lymphocytes in blood. There was significant down-regulation of CD62L (L-selectin) and CD49d (VLA-4) expression after allergen challenge on BAL eosinophils and lymphocytes compared to blood. In addition, VCAM-1 (ligand for VLA-4) was up-regulated on blood vessels of allergen-challenged lungs. Eosinophils, CD4+ T cells and CD45R+ B cells were the most prominent leucocytes found in lung tissue 48 h after allergen challenge.Conclusion This study demonstrates, for the first time, the ability of house dust mite to induce allergic responses in sheep lungs. 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Bischof, R. J. misc allergic lung inflammation Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite |
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Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite allergic lung inflammation |
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Blackwell Science Ltd |
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Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite |
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Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite |
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Bischof, R. J. Snibson, K. Shaw, R. |
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Bischof, R. J. |
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10.1046/j.1365-2222.2003.01534.x |
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induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite |
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Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite |
abstract |
Background Previous sheep models of asthma are based on sheep sensitized to nematode (Ascaris) allergens and these have been used to evaluate the physiological and pharmacological effects of potential anti-asthma agents. The immunological mechanisms associated with the allergic response in sheep lungs has not been examined in detail.Objective To develop an experimental sheep model of allergic lung inflammation based on a relevant major human allergen, house dust mite, and to define the immunological features of the allergic response in this model.Methods Sheep immunized subcutaneously with solubilized house dust mite extract were given a single bronchial challenge with house dust mite. Bronchoalveolar lavage (BAL) and peripheral blood leucocytes were collected before and after challenge for flow cytometry, and tissue samples were taken post-mortem (48 h post-challenge) for histology and immunohistochemical analyses.Results Immunizations with 50 μg house dust mite induced an allergen-specific IgE response in 50 to 60% of sheep (allergic sheep), with higher antigen doses increasing specific IgG1 but not IgE. Lung challenge of allergic sheep with house dust mite led to the initial recruitment of neutrophils (at 6 h post-challenge) followed by eosinophils and activated lymphocytes into the lung tissue and BAL, similar to the late-phase allergic response seen in human asthma. Eosinophil recruitment peaked at 48 h post-challenge, representing 10 to 33% of BAL leucocytes in allergen-challenged allergic sheep compared to 0 to 3% in allergen-challenged control (naïve) sheep. Lymphocytes recovered from the lung after allergen challenge were enriched for CD4+ T cells and were more activated than lymphocytes in blood. There was significant down-regulation of CD62L (L-selectin) and CD49d (VLA-4) expression after allergen challenge on BAL eosinophils and lymphocytes compared to blood. In addition, VCAM-1 (ligand for VLA-4) was up-regulated on blood vessels of allergen-challenged lungs. Eosinophils, CD4+ T cells and CD45R+ B cells were the most prominent leucocytes found in lung tissue 48 h after allergen challenge.Conclusion This study demonstrates, for the first time, the ability of house dust mite to induce allergic responses in sheep lungs. This novel sheep model of allergic lung inflammation using relevant human allergens, exhibits similarities to human asthmatic disease and will be a useful tool for studies of the immunological and physiological mechanisms of allergic asthma. |
abstractGer |
Background Previous sheep models of asthma are based on sheep sensitized to nematode (Ascaris) allergens and these have been used to evaluate the physiological and pharmacological effects of potential anti-asthma agents. The immunological mechanisms associated with the allergic response in sheep lungs has not been examined in detail.Objective To develop an experimental sheep model of allergic lung inflammation based on a relevant major human allergen, house dust mite, and to define the immunological features of the allergic response in this model.Methods Sheep immunized subcutaneously with solubilized house dust mite extract were given a single bronchial challenge with house dust mite. Bronchoalveolar lavage (BAL) and peripheral blood leucocytes were collected before and after challenge for flow cytometry, and tissue samples were taken post-mortem (48 h post-challenge) for histology and immunohistochemical analyses.Results Immunizations with 50 μg house dust mite induced an allergen-specific IgE response in 50 to 60% of sheep (allergic sheep), with higher antigen doses increasing specific IgG1 but not IgE. Lung challenge of allergic sheep with house dust mite led to the initial recruitment of neutrophils (at 6 h post-challenge) followed by eosinophils and activated lymphocytes into the lung tissue and BAL, similar to the late-phase allergic response seen in human asthma. Eosinophil recruitment peaked at 48 h post-challenge, representing 10 to 33% of BAL leucocytes in allergen-challenged allergic sheep compared to 0 to 3% in allergen-challenged control (naïve) sheep. Lymphocytes recovered from the lung after allergen challenge were enriched for CD4+ T cells and were more activated than lymphocytes in blood. There was significant down-regulation of CD62L (L-selectin) and CD49d (VLA-4) expression after allergen challenge on BAL eosinophils and lymphocytes compared to blood. In addition, VCAM-1 (ligand for VLA-4) was up-regulated on blood vessels of allergen-challenged lungs. Eosinophils, CD4+ T cells and CD45R+ B cells were the most prominent leucocytes found in lung tissue 48 h after allergen challenge.Conclusion This study demonstrates, for the first time, the ability of house dust mite to induce allergic responses in sheep lungs. This novel sheep model of allergic lung inflammation using relevant human allergens, exhibits similarities to human asthmatic disease and will be a useful tool for studies of the immunological and physiological mechanisms of allergic asthma. |
abstract_unstemmed |
Background Previous sheep models of asthma are based on sheep sensitized to nematode (Ascaris) allergens and these have been used to evaluate the physiological and pharmacological effects of potential anti-asthma agents. The immunological mechanisms associated with the allergic response in sheep lungs has not been examined in detail.Objective To develop an experimental sheep model of allergic lung inflammation based on a relevant major human allergen, house dust mite, and to define the immunological features of the allergic response in this model.Methods Sheep immunized subcutaneously with solubilized house dust mite extract were given a single bronchial challenge with house dust mite. Bronchoalveolar lavage (BAL) and peripheral blood leucocytes were collected before and after challenge for flow cytometry, and tissue samples were taken post-mortem (48 h post-challenge) for histology and immunohistochemical analyses.Results Immunizations with 50 μg house dust mite induced an allergen-specific IgE response in 50 to 60% of sheep (allergic sheep), with higher antigen doses increasing specific IgG1 but not IgE. Lung challenge of allergic sheep with house dust mite led to the initial recruitment of neutrophils (at 6 h post-challenge) followed by eosinophils and activated lymphocytes into the lung tissue and BAL, similar to the late-phase allergic response seen in human asthma. Eosinophil recruitment peaked at 48 h post-challenge, representing 10 to 33% of BAL leucocytes in allergen-challenged allergic sheep compared to 0 to 3% in allergen-challenged control (naïve) sheep. Lymphocytes recovered from the lung after allergen challenge were enriched for CD4+ T cells and were more activated than lymphocytes in blood. There was significant down-regulation of CD62L (L-selectin) and CD49d (VLA-4) expression after allergen challenge on BAL eosinophils and lymphocytes compared to blood. In addition, VCAM-1 (ligand for VLA-4) was up-regulated on blood vessels of allergen-challenged lungs. Eosinophils, CD4+ T cells and CD45R+ B cells were the most prominent leucocytes found in lung tissue 48 h after allergen challenge.Conclusion This study demonstrates, for the first time, the ability of house dust mite to induce allergic responses in sheep lungs. This novel sheep model of allergic lung inflammation using relevant human allergens, exhibits similarities to human asthmatic disease and will be a useful tool for studies of the immunological and physiological mechanisms of allergic asthma. |
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Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite |
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Snibson, K. Shaw, R. Meeusen, E. N. T |
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