Mono- and dihydroxyeicosatetraenoic acids alter calcium homeostasis in rabbit neutrophils.

Abstract

Products of the lipoxygenation of arachidonic acid that express neutrophil chemotactic activity were examined in vitro for effects on the uptake of 45Ca by rabbit peritoneal neutrophils. At optimally chemotactic concentrations, 5- and 11-hydroperoxyeicosatetraenoic acid, 11- and 12L-hydroxyeicosatetraenoic acid, and leukotriene B4 enhanced 45Ca uptake within 1 min by a mean of 212-694% of the values for control neutrophils incubated in buffer alone, as compared with 75% for 5(S)-hydroxyeicosatetraenoic acid and no effect for 15-hydroperoxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic acid. The approximate rank of potency of the factors stimulating 45Ca uptake was similar to that observed for chemotaxis. Leukotriene B4, in addition to stimulating the rate of 45Ca uptake into rabbit neutrophils, also displaced intracellular calcium. The net result of the leukotriene B4-induced changes in calcium homeostasis ws to elevate transiently the intracellular level of exchangeable calcium. That neutrophil lipoxygenase metabolites of endogenous arachidonic acid rapidly enhance the influx of 45Ca supports a possible role for such metabolites in general, and leukotriene B4 in particular, in the regulation of the intracellular levels of free calcium in the neutrophils and possibly in other hormonally sensitive cells in which this cation is a second messenger.