PLATELET-ACTIVATING-FACTOR INDUCED POLYMORPHONUCLEAR NEUTROPHIL PRIMING INDEPENDENT OF CD11(B) ADHESION

Background. Our previous studies have implicated phospholipase A2-depe ndent platelet-activating factor (PAF) production in the genesis of po lymorphonuclear neutrophil (PMN)-mediated tissue injury after gut isch emia-reperfusion. Further, these studies have suggested a discordance of PMN sequestration and tissue injury. CD11B-dependent PMN-endothelia l cell adhesion has been purported to play a dominant role in PMN-medi ated tissue injury. We therefore undertook this study with the hypothe sis that PAF-induced PMN superoxide production requires CD11B-mediated PMN-endothelial cell adherence. Methods. Human PMNs, isolated by Perc oll gradient centrifugation, were exposed to PAF (10 ng/ml). At fixed times of exposure during 120 minutes, (1) superoxide production, (2) C D11B receptor expression, and (3) PMN adhesion to unstimulated human u mbilical vein endothelial cell cultures were assayed. Results. PAF ind uced prompt changes in PMN priming (increased superoxide production af ter N-formyl-methyl-leucyl-phenylalanine activation), adhesion to unst imulated endothelial cells, and CD11B receptor expression. Priming was temporally concordant with the rise and fall of CD11B expression but appeared to precede adhesion. CD11B blockade (F(Ab') 2 anti-CD11B 60. 1! antibodies), before or at maximal PAF priming, reduced PMN adhesion but had no effect on superoxide production. Conclusions. In summary, PAF-induced PMN priming occurs in temporal concordance with the expres sion of CD11B and subsequent endothelial cell adherence, but CD11B-med iated adherence is not essential for this process.