The role of leukocyte beta 2-integrin in paf-induced shock and intestinal injury. Sun, Xiao-Ming, Xiao-Wu Qu, Wei Huang, D. Neil Granger, Mark Bree, and Wei Hsueh. Dept. of Pathology, Children's Memorial Hospital, Northwestern University Medical School, Chicago, IL 60614, Dept. of Physiology, LSU Medical School, Shreveport, LA 71130, and Repligen Corp., Cambridge, MA 02139
APStracts 2:0158G, 1995.
Leukocyte adhesion and diapedesis, critical steps in the inflammatory process, depend on the expression of integrin CD11b/CD18. In this study, we examined the preventive effect of monoclonal antibodies (MoAb) against CD11b (1B6), CD11a or CD18 (CL26) on PAF-induced bowel injury. Young male Sprague-Dawley rats were anesthetized, and injected with either of 2 doses of PAF (2.5 or 3 [mu]g/kg, i.v.) to induce transient hypotension and irreversible shock. Some rats were also injected (i.v.) with 1B6 (anti-CD11b), anti-CD11a, CL26 (anti -CD18), or combined anti-CD11a and 1B6, 30 min before PAF. Animals receiving a low dose of PAF developed mild hypotension, hemoconcentration, increased intestinal MPO and bowel injury after 1 hr. These effects were completely prevented by pretreatment with 1B6. A high dose of PAF induced irreversible shock and gross intestinal necrosis. Both CL26 and 1B6 were partially effective in attenuating PAF-induced bowel injury. Addition of anti-CD11a to 1B6 in the treatment further ameliorated the systemic adverse effects of PAF and intestinal injury. However, focal minor injury still developed. Anti -CD11a alone, fucoidin, or anti-P-selectin, was ineffective. Rats depleted of neutrophils were also largely protected from the adverse effects of PAF at high dose, although minor intestinal injury often persisted. We conclude that leukocyte [beta]2-integrins play an important role in PAF-induced hypotension, leukopenia, hemoconcentration, and intestinal necrosis; and that CD11b/CD18 is the main adhesion molecule involved in the pathogenesis of injury. However, CD11/CD18- and neutrophil-independent pathways exist for mediating PAF-induced bowel injury, although their role is probably a minor one. 

Received 30 December 1994; accepted in final form 21 July 1995.
APS Manuscript Number G570-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.