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
Ac. Nicholson et al., 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, Arteriosclerosis, thrombosis, and vascular biology, 15(2), 1995, pp. 269-275
Accumulating evidence strongly implicates oxidized LDL (Ox-LDL) in the
pathogenesis of atherosclerosis. Several receptors have been identifi
ed 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 th
at has been implicated as a putative receptor for Ox-LDL. We demonstra
te that an anti-CD36 monoclonal antibody inhibited 50% of the specific
binding and 26% of the specific degradation of Ox-LDL by human monocy
te-derived macrophages. To characterize more completely this binding w
e evaluated interactions between CD36 and Ox-LDL in murine NIH-3T3 cel
ls stably transfected with human CD36 cDNA. Ox-LDL bound to CD36-trans
fected 3T3 cells in a saturable manner. Specific binding, internalizat
ion, and degradation of Ox-LDL were increased fourfold in CD36-transfe
cted cell lines compared with 3T3 cells transfected with vector alone.
Binding of Ox-LDL to CD36-transfected 3T3 cells was inhibited by a pa
nel of anti-CD36 antibodies and by soluble CD36 but not by thrombospon
din. 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. Tw
o observations suggest that CD36 recognizes a lipid moiety or that the
lipid portion of the lipoprotein is essential for apoprotein recognit
ion. The first is that the increased binding of Ox-LDL to CD36-transfe
cted 3T3 cells is abrogated by delipidation of the lipoprotein, and th
e second is that oleic acid competes for the binding of Ox-LDL to CD36
-transfected 3T3 cells. These data demonstrate that CD36 functions as
an Ox-LDL receptor and suggest that CD36 may play a functional role in
lipid accumulation by human macrophages and subsequent foam cell deve
lopment during atherosclerosis.