APStracts 2:0112L, 1995.

Intratracheal injection of endotoxin and cytokines: ix: the contribution of cd11a / icam-1 to neutrophil emigration. Tang, Winson, Eunhee S. Yi, Daniel G. Remick, Arthur Wittwer, Songmei Yin, Meiying Qi, Thomas R. Ulich. Amgen, Thousand Oaks, CA 91320, Department of Pathology, UC San Diego School of Medicine, San Diego, CA 92103, Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI 48109, Monsanto Research, St. Louis, MO 63167

APStracts 2:0112L, 1995.

Intratracheal injection of endotoxin (LPS) in rats causes acute inflammation characterized by the emigration of neutrophils (PMNs) into the bronchoalveolar airspace. Antibody to PMN adhesion molecule CD11a inhibited LPS-initiated PMN accumulation in bronchoalveolar lavage (BAL) fluid by 32% (p&LT0.001). Antibody to the endothelial CD11a counterreceptor ICAM-1 inhibited LPS-initiated PMN accumulation in BAL fluid by 66% (p&LT0.0001). Combined antibody blockade of ICAM-1 and the C-X-C chemokine CINC inhibited LPS-initiated PMN emigration by 80%, significantly more than antibody against either ICAM-1 or CINC alone. The study the relative contribution of alveolar macrophages and PMNs to intraalveolar TNF, the LPS-induced TNF in BAL fluid was measured after depletion of circulating PMNs with a cytolytic antibody to CD18. Although the anti-CD18 antibody completely abrogated LPS-initiated PMN emigration into BAL fluid, TNF levels in BAL fluid were unaffected, suggesting that alveolar macrophages are the predominant cellular source of LPS-induced TNF production. In conclusion, 1) CD11a, ICAM-1, and CINC play major roles in the LPS-initiated emigration of PMNs into the bronchoalveolar space, and 2) the TNF that drives ICAM-1 and CINC expression is derived largely from alveolar macrophages rather than PMNs.

Received 13 December 1994; accepted in final form 19 June 1995.
APS Manuscript Number L355-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 11 July 1995.