The binding of oxidized low density lipoprotein to mouse CD36 is mediated in part by oxidized phospholipids that are associated with both the lipid and protein moieties of the lipoprotein

There is growing evidence that CD36 has an important physiological function in the uptake of oxidized low density lipoprotein (OxLDL) by macrophages, However, the ligand specificity and the nature of the ligands on OxLDL that mediate the binding to CD36 remain ill defined, Results from recent studie s suggested that some of the macrophage scavenger receptors involved in the uptake of OxLDL recognized both the lipid and the protein moieties of OxLD L, but there was no conclusive direct evidence for this. The present studie s were undertaken to test whether a single, well characterized OzLDL recept or, CD36, could bind both the lipid and protein moieties of OxLDL, COS-7 ce lls transiently transfected with mouse CD36 cDNA bound intact OxLDL with hi gh affinity. This binding was very effectively inhibited (similar to 50%) b oth by the reconstituted apoB from OxLDL and by microemulsions prepared fro m OxLDL lipids. The specific binding of both moieties to CD36 was further c onfirmed by direct ligand binding analysis and by demonstrating reciprocal inhibition, i.e. apoB from OxLDL inhibited the binding of the OxLDL lipids and vice versa. Furthermore, a monoclonal mouse antibody that recognizes ox idation-specific epitopes in OxLDL inhibited the binding of intact OxLDL an d also that of its purified protein and lipid moieties to CD36, This antibo dy recognizes the phospholipid l-palmitoyl 2-(5'-oxovaleroyl) phosphatidylc holine, This model of an oxidized phospholipid was also an effective compet itor for the CD36 binding of both the resolubilized apoB and the lipid micr oemulsions from OxLDL, Our results demonstrate that oxidized phospholipids in the lipid phase or covalently attached to apoB serve as ligands for reco gnition by CD36 and, at least in part, mediate the high affinity binding of OxLDL to macrophages.