Modulation of Cytotoxic Processes by Platelet-Activating Factor

Abstract

The effect of platelet-activating factor (PAF) on rat NK cell activity, rat macrophage cytotoxicity and TNF production by rat macrophages and human monocytes was investigated. After a 4-h incubation period, PAF enhanced rat NK cell activity at the effector/target cell ratios of 50/1 and 25/1 in a bell-shape fashion and with a peak effect at 1 nM. After 24 h incubation with 1 μM PAF, rat macrophage cytotoxicity, as assessed at the 20/1 effector/target cell ratio, was also increased. Addition of PAF and lipopolysaccharide (LPS) to rat macrophages or human monocytes markedly enhanced TNF production, whereas PAF alone was ineffective. This enhancement of the LPS-induced TNF production by PAF followed a bell-shape pattern and significant increases were noted at the 30 μM and 1 μM concentrations, as compared the release observed with human monocytes and rat macrophages stimulated with LPS alone, respectively. The effect of PAF on the LPS-induced TNF release from human monocytes appears to be mediated via the interaction of the autacoid with a specific receptor. Indeed, addition of the PAF antagonist, BM 52021 (10 μM), to the incubation medium inhibited by about 50% the enhancing effect fo the autacoid. The bulk of these results indicate that PAF may play a regulatory role in various cytotoxic processes.