The puzzling ligands for scavenger receptors
The conversion of arterial macrophages to foam cells is believed to occur primarily because of the uptake of oxidatively modified LDL by one or more so-called scavenger receptors. Because atherosclerosis, being a disease confined to humans and occurring late in life, cannot exert any genetic pressure, the persistence of these genes in evolution must relate to other ligands that they recognize. We have previously suggested that one vital biological process for which these receptors may be “designed” is the recognition and uptake of apoptotic cells. One well-established basis for receptor recognition of apoptotic cells is the appearance of phosphatidylserine on the outer leaflet of the membrane (which normally expresses very little of it). This led us to reexamine the possibility that the oxidized lipid moieties of oxidized LDL might somehow mimic membranes rich in phosphatidylserine and account, at least in part, for macrophage recognition and uptake of oxidized LDL. We have now shown that indeed the lipid moiety of oxidized LDL, when reconstituted into a microemulsion free of protein, is capable of competing for binding and uptake of intact oxidized LDL by mouse resident peritoneal macrophages. The isolated protein moiety of oxidized LDL had been shown previously to compete also with intact oxidized LDL. We now suggest that the binding of apoprotein B is based upon the covalent linkage to the apoprotein of oxidized phospholipids generated during the oxidation of LDL.
KeywordsScavenger Receptor Mouse Peritoneal Macrophage Lipid Moiety Macrophage Receptor Apoptotic Thymocyte
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