Antibody to very late activation antigen 4 prevents antigen-induced bronchial hyperreactivity and cellular infiltration in the guinea pig airways.
Open Access
- 1 September 1994
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 180 (3), 795-805
- https://doi.org/10.1084/jem.180.3.795
Abstract
This report examines the effect of an anti-VLA-4 monoclonal antibody (mAb) HP1/2 on antigen-induced bronchial hyperreactivity to methacholine, and on eosinophil and T lymphocyte infiltration in the airways of guinea pigs sensitized and challenged by aerosolized ovalbumin and used 24 h thereafter. The intravenous administration of 2.5 mg/kg of HP1/2, but not of its isotype-matched mAb 1E6, 1 h before and 4 h after antigen inhalation, markedly inhibited the increased bronchopulmonary responses to intravenous methacholine, as well as airway eosinophilia in bronchoalveolar lavage (BAL) fluid and in bronchial tissue. HP1/2 also suppressed the antigen-induced infiltration of the bronchial wall by CD4+ and CD8+ T lymphocytes, identified by immunohistochemical technique using specific mAbs that recognize antigenic epitopes of guinea pig T cells. Treatment with HP1/2 also resulted in a significant increase in the number of blood eosinophils, suggesting that inhibition by anti-VLA-4 mAb of eosinophil recruitment to the alveolar compartment may partially account for their accumulation in the circulation. These findings indicate that eosinophil and lymphocyte adhesion and subsequent infiltration into the guinea pig airways that follow antigen challenge are mediated by VLA-4. Furthermore, concomitant inhibition of antigen-induced bronchial hyperreactivity and of cellular infiltration by anti-VLA-4 mAb suggests a relationship between airway inflammation and modifications in the bronchopulmonary function.Keywords
This publication has 44 references indexed in Scilit:
- A monoclonal antibody recognizing very late activation antigen-4 inhibits eosinophil accumulation in vivo.The Journal of Experimental Medicine, 1993
- T cells and eosinophils in the pathogenesis of asthmaImmunology Today, 1992
- Predominant TH2-like Bronchoalveolar T-Lymphocyte Population in Atopic AsthmaNew England Journal of Medicine, 1992
- Sputum eosinophils from asthmatics express ICAM-1 and HLA-DRClinical and Experimental Immunology, 1991
- Endothelial leukocyte adhesion molecule-1 mediates antigen-induced acute airway inflammation and late-phase airway obstruction in monkeys.JCI Insight, 1991
- VLA Proteins in the Integrin Family: Structures, Functions, and Their Role on LeukocytesAnnual Review of Immunology, 1990
- Intercellular Adhesion Molecule-1 (ICAM-1) in the Pathogenesis of asthmaScience, 1990
- Identification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin.The Journal of cell biology, 1989
- The Severe and Moderate Phenotypes of Heritable Mac-1, LFA-1 Deficiency: Their Quantitative Definition and Relation to Leukocyte Dysfunction and Clinical FeaturesThe Journal of Infectious Diseases, 1985
- The identification of eosinophil colonies in soft-agar cultures by differential staining for peroxidase.Journal of Histochemistry & Cytochemistry, 1976