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 Citations (Scopus)

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
Pages (from-to)97-104
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume169
Issue number1
StatePublished - Jan 1 2004
Externally publishedYes

Fingerprint

Sheep
Monoclonal Antibodies
Antigens
Integrins
Allergens
Integrin alpha1beta1
Pathology
Mononuclear Leukocytes
Fc Receptors
Lung Diseases
Monocytes
Collagen
Lymphocytes
Inflammation
Antibodies

Keywords

  • Animal model
  • Asthma
  • CD49a
  • Inflammation
  • Integrin

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Abraham, W. M., Ahmed, A., Serebriakov, I., Carmillo, A. N., Ferrant, J., De Fougerolles, A. R., ... 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.

A Monoclonal Antibody to α1β1 Blocks Antigen-induced Airway Responses in Sheep. / Abraham, William M.; Ahmed, Ashfaq; Serebriakov, Irakli; Carmillo, Amie N.; Ferrant, Janine; De Fougerolles, Antonin R.; Garber, Ellen A.; Gotwals, Philip J.; Koteliansky, Victor E.; Taylor, Fred; Lobb, Roy R.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 169, No. 1, 01.01.2004, p. 97-104.

Research output: Contribution to journalArticle

Abraham, WM, Ahmed, A, Serebriakov, I, Carmillo, AN, Ferrant, J, De Fougerolles, AR, Garber, EA, Gotwals, PJ, Koteliansky, VE, Taylor, F & Lobb, RR 2004, 'A Monoclonal Antibody to α1β1 Blocks Antigen-induced Airway Responses in Sheep', American Journal of Respiratory and Critical Care Medicine, vol. 169, no. 1, pp. 97-104.
Abraham WM, Ahmed A, Serebriakov I, Carmillo AN, Ferrant J, De Fougerolles AR et al. A Monoclonal Antibody to α1β1 Blocks Antigen-induced Airway Responses in Sheep. American Journal of Respiratory and Critical Care Medicine. 2004 Jan 1;169(1):97-104.
Abraham, William M. ; Ahmed, Ashfaq ; Serebriakov, Irakli ; Carmillo, Amie N. ; Ferrant, Janine ; De Fougerolles, Antonin R. ; Garber, Ellen A. ; Gotwals, Philip J. ; Koteliansky, Victor E. ; Taylor, Fred ; Lobb, Roy R. / A Monoclonal Antibody to α1β1 Blocks Antigen-induced Airway Responses in Sheep. In: American Journal of Respiratory and Critical Care Medicine. 2004 ; Vol. 169, No. 1. pp. 97-104.
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