Interactions between synthesis of platelet-activating factor and leukotriene B4 in isolated human polymorphonuclear leukocytes

Abstract

The aim of the present work was to study interactions between the synthesis of platelet-activating factor (PAF) and leukotriene B4 (LTB4) in human polymorphonuclear leukocytes (PMNs) in vitro. PAF, at nanomolar concentrations, stimulated calcium ionophore A23187-activated PMNs to release LTB4 and 5-hydroxyeicosatetraenoic acid (5-HETE). This seems to be a receptor-mediated process as it was blocked by a PAF receptor antagonist WEB 2086 (IC50 6.6 +/- 3.9 microM). Moreover, LTB4 stimulated the formation of PAF in activated PMNs. WEB 2086 did not, however, alter PMN migration towards either LTB4 or the chemotactic peptide FMLP. This suggests that the enhancement of PAF synthesis in response to LTB4 is a concomitant event rather than a mediating process in LTB4-induced chemotactic movement of PMNs. These effects are implicated in the complex network of interactions between inflammatory mediators that results accumulation and activation of PMNs in the exacerbation of inflammatory processes.