Demonstration that platelet-activating factor is capable of activating mast cells and inducing a chemotactic response

Platelet-activating factor (PAF) is generated in a variety of inflammatory conditions in which mast cells accumulate. However, little is known about t he ability of PAF to influence mast cell function directly. In this study w e examine the ability of PAF to activate mast cells and regulate mast cell chemotaxis. PAF was found to induce intracellular calcium mobilization and chemotactic responses in both murine and human mast cells. PAF induced tran sient increases in intracellular Ca2+ concentrations with a 50% effective d ose of 1 nm and induced significant migratory responses at PAF concentratio ns of 1 nm to 1 mu m in the human leukaemia mast cell line (HMC-1). Using s ignal transduction inhibitors, both PAF-induced calcium mobilization and mi gration of mast cells were shown to require activation of pertussis toxin-s ensitive G proteins. PAF-induced calcium and chemotactic responses were cro ss-desensitized by C5a. Together, these data demonstrate that PAF is capabl e of activating distinct signalling pathways in mast cells associated with calcium mobilization and cell migration; and that PAF may thus contribute t o the regulation of mast cell responses and hyperplasia at sites of inflamm ation.