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

Citation
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
Citations number
45
Categorie Soggetti
Cardiac & Cardiovascular System","Peripheal Vascular Diseas
ISSN journal
10795642
Volume
15
Issue
2
Year of publication
1995
Pages
269 - 275
Database
ISI
SICI code
1079-5642(1995)15:2<269:OLBTCO>2.0.ZU;2-5
Abstract
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.