Involvement of Group VIA Calcium-Independent Phospholipase A2 in Macrophage Engulfment of Hydrogen Peroxide-Treated U937 Cells

摘要

Hydrogen peroxide-induced apoptosis of U937 cells results in substantial hydrolysis of membrane phospholipids by calcium-independent group VIA phospholipase A2 (iPLA2-VIA). However, abrogation of cellular iPLA2-VIA neither delays nor decreases apoptosis, suggesting that, beyond a mere destructive role, iPLA2-VIA may serve other specific roles. In this study, we report that phagocytosis of apoptosing U937 cells by macrophages is blunted if the cells are depleted of iPLA2-VIA by treatment with an inhibitor or an antisense oligonucleotide, and it is augmented by overexpression of iPLA2-VIA in the dying cells. Thus, the magnitude of macrophage phagocytosis correlates with the level of iPLA2-VIA activity of the dying cells. Eliminating by antisense oligonucleotide technology of cytosolic group IVA phospholipase A2 does not attenuate phagocytosis of U937 dying cells by macrophages. Incubation of U937 cells with different fatty acids has no effect on either the extent of hydrogen peroxide-induced apoptosis or the degree of phagocytosis of the dying cells by macrophages. However, preincubation of the macrophages with lysophosphatidylcholine before exposing them to the dying cells blocks phagocytosis of the latter. These results indicate that formation of lysophosphatidylcholine by iPLA2-VIA in hydrogen peroxide-treated U937 cells to induce apoptosis directly contributes to their efficient clearance by macrophages.