Role of intercellular adhesion molecule-1 in antigen-induced lung
inflammation in brown norway rats.
Richards, Ivan M., Karen P. Kolbasa, Greg E. Winterrowd, Cheryl A.
Hatfield, Steven L. Vonderfecht, Stephen F. Fidler, Robert L.
Griffin, John R. Brashler, Raymond F. Krzesicki, Caryl L. Lane,
Donald C. Anderson, Laurel M. Sly, Nigel D. Staite, and Jia En Chin.
Cell Biology and Inflammation Research and Drug Development
Toxicology, Upjohn Laboratories, Kalamazoo, MI 49001
APStracts 3:0093L, 1996.
We investigated the involvement of intercellular adhesion molecule-1
(ICAM-1; CD54) in ovalbumin (OA) antigen-induced lung inflammation in
sensitized Brown Norway (BN) rats, by using flow cytometry and in
vivo treatment with a murine monoclonal antibody (mAb), 1A29,
directed against rat ICAM-1. OA-challenge induced an eosinophil and
lymphocyte-rich accumulation of leukocytes into the airway lumen.
Between 75-90% of the T cells in bronchoalveolar lavage (BAL) fluid
after challenge, expressed CD54 and CD11a, and were of the memory
phenotype. 1A29 treatment produced dose-related increases in
circulating 1A29, and blood neutrophils. In the BAL fluid of 1A29
-treated animals, significant (p<0.05) reductions in the numbers
of eosinophils and lymphocytes, but not neutrophils or alveolar
macrophages were observed, in association with a reduced inflammatory
pathology in lung tissue. 1A29-administration reduced the number of
detectable ICAM-1 binding sites on T cells in peripheral blood and
BAL fluid examined ex vivo by flow cytometry. We conclude that ICAM-1
is critically important for the antigen-specific recruitment of
eosinophils and lymphocytes into the lungs.
Received 1 December 1995; accepted in final form 19 March 1996.
APS Manuscript Number L353-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 17 June 96