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

Abstract

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 greater than 5 nM PAF. In contrast, leukotriene B4 (LTB4), 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 LTB4-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 LTB4. This LTB4 in turn elicits a secondary rise in calcium, which contributes to the overall response of neutrophils of PAF. These results demonstrate how LTB4 participates in the cellular responses elicited by PAF in human neutrophils.