Platelet-activating factor-induced polymorphonuclear neutrophil priming independent of CD11b adhesion.

BACKGROUND

Our previous studies have implicated phospholipase A2-dependent platelet-activating factor (PAF) production in the genesis of polymorphonuclear neutrophil (PMN)-mediated tissue injury after gut ischemia-reperfusion. Further, these studies have suggested a discordance of PMN sequestration and tissue injury. CD11B-dependent PMN-endothelial cell adhesion has been purported to play a dominant role in PMN-mediated tissue injury. We therefore undertook this study with the hypothesis that PAF-induced PMN superoxide production requires CD11B-mediated PMN-endothelial cell adherence.

METHODS

Human PMNs, isolated by Percoll gradient centrifugation, were exposed to PAF (10 ng/ml). At fixed times of exposure during 120 minutes, (1) superoxide production, (2) CD11B receptor expression, and (3) PMN adhesion to unstimulated human umbilical vein endothelial cell cultures were assayed.

RESULTS

PAF induced prompt changes in PMN priming (increased superoxide production after N-formyl-methyl-leucyl-phenylalanine activation), adhesion to unstimulated 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 expression of CD11B and subsequent endothelial cell adherence, but CD11B-mediated adherence is not essential for this process.