INTERACTIONS BETWEEN SYNTHESIS OF PLATELET-ACTIVATING-FACTOR AND LEUKOTRIENE-B(4) IN ISOLATED HUMAN POLYMORPHONUCLEAR LEUKOCYTES

The aim of the present work was to study interactions between the synt hesis 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 muM). Moreover, LTB4 stimulated the formation of PAF in activated PMNs. WEB 2086 did not, however, alt er PMN migration towards either LTB4 or the chemotactic peptide FMLP. This suggests that the enhancement of PAF synthesis in response to LTB 4 is a concomitant event rather than a mediating process in LTB4-induc ed chemotactic movement of PMNs. These effects are implicated in the c omplex network of interactions between inflammatory mediators that res ults accumulation and activation of PMNs in the exacerbation of inflam matory processes.