A Monoclonal Antibody to α1β1 Blocks Antigen-induced Airway Responses in Sheep

William M. Abraham, Ashfaq Ahmed, Irakli Serebriakov, Amie N. Carmillo, Janine Ferrant, Antonin R. De Fougerolles, Ellen A. Garber, Philip J. Gotwals, Victor E. Koteliansky, Fred Taylor, Roy R. Lobb

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

The integrin α1β1 (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 α1β1 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 ai 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 IgC1 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 ai integrins may be useful in preventing these events.

Original languageEnglish (US)
Pages (from-to)97-104
Number of pages8
JournalAmerican journal of respiratory and critical care medicine
Volume169
Issue number1
DOIs
StatePublished - Jan 1 2004

Keywords

  • Animal model
  • Asthma
  • CD49a
  • Inflammation
  • Integrin

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Fingerprint Dive into the research topics of 'A Monoclonal Antibody to α1β1 Blocks Antigen-induced Airway Responses in Sheep'. Together they form a unique fingerprint.

  • Cite this

    Abraham, W. M., Ahmed, A., Serebriakov, I., Carmillo, A. N., Ferrant, J., De Fougerolles, A. R., Garber, E. A., Gotwals, P. J., Koteliansky, V. E., Taylor, F., & Lobb, R. R. (2004). A Monoclonal Antibody to α1β1 Blocks Antigen-induced Airway Responses in Sheep. American journal of respiratory and critical care medicine, 169(1), 97-104. https://doi.org/10.1164/rccm.200304-543oc