Platelet-activating factor primes neutrophil responses to agonists: Role in promoting neutrophil-mediated endothelial damage

G. M. Vercellotti, H. Q. Yin, K. S. Gustafson, R. D. Nelson, H. S. Jacob

Research output: Contribution to journalArticlepeer-review

193 Scopus citations

Abstract

During inflammation polymorphonuclear cells (PMNs) are exposed to agonistic stimuli including acitvated complement, kallikrein, arachidonic acid metabolites, monokines, and platelet-activating factor (PAF). We report that PAF not only directly activates PMNs but in miniscule quantities (10-12 mol/L) 'primes' them as well, that is, permits PMNs to respond to subsequent stimuli that would be otherwise ineffectual. PAF priming of responses including superoxide generation, elastase release, and aggregation is time dependent and is maximal within five minutes. PAF need not be present during the subsequent exhibition of PMN agonists, but priming is inhibited by cold and is also inhibited by the PAF receptor antagonists BN 52021, L-652, and kadsurenone. An intact PAF molecule is required because lyso-PAF and methoxy-PAF do not prime PMN responses. PAF priming is associated with both enhanced expression of the adhesive glycoprotein identified by OKM-1 antibody and an enhanced rise in intracellular calcium levels in response to the subsequent addition of agonists such as FMLP. PMNs primed with PAF and stimulated with either F-Met-Leu-Phe or phorbol esters are more effective in lysing and detaching cultured human endothelial cells-damage that can also be inhibited by the PAF antagonists. Because PAF is synthesized and exhibited on surfaces of endothelial cells perturbed by coagulation, we suggest that this lipid may potentiate otherwise trivial activators of marginated PMNs so that they become damaging to the PAF-synthesizing endothelium itself. If so, our studies suggest a possible therapeutic role for PAF inhibitors in excessive inflammatory states.

Original languageEnglish (US)
Pages (from-to)1100-1107
Number of pages8
JournalBlood
Volume71
Issue number4
DOIs
StatePublished - 1988

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