Oxidized low-density lipoprotein induces calcium influx in polymorphonuclear leukocytes

Polymorphonuclear leukocytes (PMN) have been suggested to play a role in at herosclerosis, but intracellular signaling after stimulation with oxidized low-density Lipoprotein (LDL) is unknown. We investigated mechanistic aspec ts of oxidized LDL-induced superoxide production by human PMN, with special emphasis on intracellular Ca2+ concentration ([Ca2+](i)). Oxidized LDL, bu t not native LDL, evoked an early but sustained increase in [Ca2+](i) and a delayed production of superoxide. The increase in [Ca2+](i) could be reduc ed by fucoidan and completely prevented by U73122, suggesting involvement o f the scavenger receptor and coupling to the phospholipase C signal transdu ction pathway. Furthermore, we provide evidence that the increase in [Ca2+] (i) partly results from protein kinase C-dependent Ca2+ influx. The relevan ce of this Ca2+ entry for oxidized LDL-stimulated effects is illustrated by the finding that superoxide production was markedly reduced in the absence of external Ca2+. Finally, inhibition of phagocytosis by cytochalasin B ab olished oxidized LDL-stimulated superoxide production without affecting, ho wever, the Ca2+ mobilization. These effects of oxidized LDL on [Ca2+](i) an d on respiratory burst of PMN may underlie the occurrence of elevated level s of [Ca2+](i) of resting PMN in hypercholesterolemia and represent a mecha nism by which PMN can amplify processes in the early phase of atheroscleros is. (C) 2000 Elsevier Science Inc.