A Monoclonal Antibody to α1β1 Blocks Antigen-induced Airway Responses in Sheep
| Autor: | Amie N. Carmillo, Victor Koteliansky, Ashfaq Ahmed, Roy R. Lobb, Frederick R. Taylor, Philip Gotwals, Ellen Garber, William M. Abraham, Janine Ferrant, Antonin de Fougerolles, Irakli Serebriakov |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Integrins medicine.drug_class Inflammation Critical Care and Intensive Care Medicine Monoclonal antibody Sensitivity and Specificity Bronchial Provocation Tests CD49a Antigen Receptors Very Late Antigen Reference Values Intensive care Administration Inhalation medicine Animals Receptor Sheep Domestic Probability biology business.industry Airway Resistance Antibodies Monoclonal CD29 Disease Models Animal Immunology biology.protein Female Bronchial Hyperreactivity Antibody medicine.symptom business |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine. 169:97-104 |
| ISSN: | 1535-4970 1073-449X |
| Popis: | The integrin alpha1beta1 (very late antigen-1; CD49a/CD29) is a major adhesion receptor for collagen I, IV, and VI, and its induced expression on activated monocytes and lymphocytes plays a central role in their retention and activation at inflammatory sites in autoimmune pathologies. However, the role of alpha1beta1 in allergic settings has not been explored. In this study, we show that a single 45-mg dose of aerosolized monoclonal antibody AQC2 to the alpha1 chain of human and sheep very late antigen-1, given 30 minutes before challenge, blocks both the allergen-induced late response and the associated airway hyperresponsiveness, functional indicators of allergen-induced inflammation, in sheep. AQC2 does not affect the early response. Consistent with these effects, AQC2 tended to reduce the cell response associated with local antigen instillation. An isotype-matched control antibody had no protective effects. Two humanized versions of AQC2, a wild-type IgG1 and an aglycosyl form of the same monoclonal antibody, which has reduced Fc receptor-mediated effector functions, are equally effective in blocking the antigen-induced late response and airway hyperresponsiveness in the sheep model. These data suggest that mononuclear leukocyte adhesion-dependent pathologies contribute to allergic lung disease and provide proof-of-concept that antagonists of alpha1 integrins may be useful in preventing these events. |
| Databáze: | OpenAIRE |
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