IMMUNOGLOBULIN G-MEDIATED PHAGOCYTOSIS ACTIVATES A CALCIUM-INDEPENDENT, PHOSPHATIDYLETHANOLAMINE-SPECIFIC PHOSPHOLIPASE

Inhibition of arachidonate release down-regulates immunoglobulin G-mediated phagocytosis This arachidonate requirement is selective for IgG opsonized targets, suggesting that arachidonate may act as a second messenger for Fc-gamma receptor-mediated phagocytosis. Here we report the characterization of a phospholipase, activated during phagocytosis, that releases arachidonate from phosphatidylethanolamine in the absence of intracellular calcium ([Ca]i less-than-or-equal-to 2 nM). In vitro, a phospholipase with these characteristics was detected in soluble and particulate fractions of human monocyte homogenates. (E)-6-(Bromomethylene)tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one, a drug that selectively inhibits Ca-independent phospholipase A2S, is shown to inhibit IgG-mediated phagocytosis and its associated arachidonate release in intact monocytes as well as the in vitro enzyme activity. These findings provide a link between the whole-cell and in vitro data and present the initial characterization of a receptor-activated, calcium-independent phospholipase from human monocytes.