RESPECTIVE ROLE OF POLYMORPHONUCLEAR LEUKOCYTES AND THEIR INTEGRINS (CD-11 18) IN THE LOCAL OR SYSTEMIC TOXICITY OF LIPOPOLYSACCHARIDE/

The role of neutrophils (PMNs) and leukocyte integrins was investigate d in two models of lipopolysaccharide (LPS)-induced toxicity: the syst emic lethality assay in D-galactosamine-sensitized mice and the local reaction elicited by intradermal injection of LPS and tumor necrosis f actor (TNF) at 24-h intervals. In the local reaction, depletion of PMN s with an anti-PMN monoclonal antibody (mAb) and mAbs against CD-11a ( or LFA1) and CD-11b (or CR3) completely prevented the hemorrhagic necr osis. Evaluation of histological sections and myeloperoxidase levels s uggested different mechanism of protection because PMNs were abundant in anti-CD11- and absent in anti-PMN-treated mice. In the systemic ass ay, depletion of PMNs ensured 100% survival, whereas after administrat ion of anti-CD-11a or b mAb, the percentages of survivors were 6 and 5 9%, respectively. One hour after LPS injection, the serum TNF-alpha le vel was higher in PMN-depleted mice than in controls. These studies pr ovide evidence that neutrophils are essential for the expression of lo cal or systemic LPS-induced injury, whereas the requirement for their leukocytic integrins is obvious only in the local reaction.