Platelet activating factor stimulates intracellular calcium transients in human neutrophils: involvement of endogenous 5‐lipoxygenase products

Stimulation of human neutrophils with platelet activating factor (PAF) resulted in a transient elevation of free cytosolic calcium. Neutrophils exhibited a two‐component calcium response observed as a double peak when stimulated with > 5 nM PAF. In contrast, leukotriene B 4 (LTB 4 ), C5a, or formylmethionyl‐leucyl‐phenylalanine stimulated only a single‐peak calcium response. The double‐peak calcium response was not elicited in human monocytes or differentiated U937 cells, which demonstrated a single peak. Pretreatment of neutrophils with a 5‐lipoxygenase inhibitor or a specific LTB 4 ‐receptor antagonist selectively blocked the second calcium peak. These results suggest that PAF‐mediated activation of human neutrophils results in the activation of the 5‐lipoxygenase and the subsequent generation of LTB 4 . This LTB 4 in turn elicits a secondary rise in calcium, which contributes to the overall response of neutrophils to PAF. These results demonstrate how LTB 4 participates in the cellular responses elicited by PAF in human neutrophils.