RECOGNITION OF OXIDATIVELY DAMAGED AND APOPTOTIC CELLS BY AN OXIDIZEDLOW-DENSITY-LIPOPROTEIN RECEPTOR ON MOUSE PERITONEAL-MACROPHAGES - ROLE OF MEMBRANE PHOSPHATIDYLSERINE

We recently reported that oxidized low density lipoprotein (OxLDL), bu t not acetyl LDL (AcLDL), inhibited the binding and phagocytosis of no nopsonized, oxidatively damaged red blood cells (OxRBCs) by mouse peri toneal macrophages, implying the involvement of a ''scavenger receptor '' other than the AcLDL receptor. Numerous studies establish that loss of plasma membrane phospholipid asymmetry, which increases phosphatid ylserine expression on the outer leaflet of the membrane, can play a k ey role in macrophage recognition of damaged and apoptotic cells. We r eport here that this recognition is in part attributable to the same m ouse macrophage receptor that recognizes OxLDL. As described in an acc ompanying paper, this is a plasma membrane protein of 94-97 kDa. Phosp hatidylserine liposomes show strong ligand binding to the same 94- to 97-kDa protein and this binding is inhibited by OxLDL but not by AcLDL . Inhibition of the RBC membrane phospholipid translocase by incubatio n with sodium vanadate caused a progressive increase in the appearance of phosphatidylserine on the cell surface and a parallel increase in the binding of these RBCs to macrophages, binding that was inhibited b y OxLDL, Finally, OxLDL also inhibited the binding of sickled RBCs and apoptotic thymocytes to mouse macrophages. However, the latter was in complete (approximate to 50%), suggesting that other receptors are als o involved, We suggest that the OxLDL receptor plays a significant rol e in recognition of damaged and apoptotic cells.