Oxidized low-density lipoprotein induces calcium influx in polymorphonuclear leukocytes

Polymorphonuclear leukocytes (PMN) have been suggested to play a role in atherosclerosis, but intracellular signaling after stimulation with oxidized low-density lipoprotein (LDL) is unknown. We investigated mechanistic aspects of oxidized LDL-induced superoxide production by human PMN, with special emphasis on intracellular Ca2+ concentration ([Ca2+]i). Oxidized LDL, but 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 reduced by fucoidan and completely prevented by U73122, suggesting involvement of the scavenger receptor and coupling to the phospholipase C signal transduction pathway. Furthermore, we provide evidence that the increase in [Ca2+]i partly results from protein kinase C–dependent Ca2+ influx. The relevance 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 abolished oxidized LDL-stimulated superoxide production without affecting, however, the Ca2+ mobilization. These effects of oxidized LDL on [Ca2+]i and on respiratory burst of PMN may underlie the occurrence of elevated levels of [Ca2+]i of resting PMN in hypercholesterolemia and represent a mechanism by which PMN can amplify processes in the early phase of atherosclerosis.