Oxidized LDL binds to CD36 on human monocyte-derived macrophages and transfected cell lines. Evidence implicating the lipid moiety of the lipoprotein as the binding site.
Accumulating evidence strongly implicates oxidized LDL (Ox-LDL) in the pathogenesis of atherosclerosis. Several receptors have been identified that bind and internalize Ox-LDL, but their relative importance in vivo is unclear. CD36 is an 88-kD transmembrane glycoprotein expressed on monocytes/macrophages, platelets, and microvascular endothelium that has been implicated as a putative receptor for Ox-LDL. We demonstrate that an anti-CD36 monoclonal antibody inhibited 50% of the specific binding and 26% of the specific degradation of Ox-LDL by human monocyte-derived macrophages. To characterize more completely this binding we evaluated interactions between CD36 and Ox-LDL in murine NIH-3T3 cells stably transfected with human CD36 cDNA. Ox-LDL bound to CD36-transfected 3T3 cells in a saturable manner. Specific binding, internalization, and degradation of Ox-LDL were increased fourfold in CD36-transfected cell lines compared with 3T3 cells transfected with vector alone. Binding of Ox-LDL to CD36-transfected 3T3 cells was inhibited by a panel of anti-CD36 antibodies and by soluble CD36 but not by thrombospondin. Specificity of binding was demonstrated by the equivalent binding of LDL and acetylated LDL to control and CD36-transfected 3T3 cells. The epitope or epitopes on Ox-LDL recognized by CD36 are undefined. Two observations suggest that CD36 recognizes a lipid moiety or that the lipid portion of the lipoprotein is essential for apoprotein recognition. The first is that the increased binding of Ox-LDL to CD36-transfected 3T3 cells is abrogated by delipidation of the lipoprotein, and the second is that oleic acid competes for the binding of Ox-LDL to CD36-transfected 3T3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Nicholson
A C
AC
Cornell University Medical College, Department of Pathology, New York, NY 10021, USA.
Frieda
S
S
Pearce
A
A
Silverstein
R L
RL
D016475:3T3 Cells; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D018955:CD36 Antigens; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D018014:Gene Transfer Techniques; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000378:metabolism; D010084:Oxidation-Reduction; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; D018955:CD36 Antigens; D018076:DNA, Complementary; D008077:Lipoproteins, LDL; D011973:Receptors, LDL