Scavenger receptors, oxidized LDL, and atherosclerosis.
Oxidized LDL (OxLDL) competes with oxidatively damaged and apoptotic cells for binding to mouse peritoneal macrophages, implying the presence of one or more common domains. However, the nature of the ligands involved has not been determined. Studies in this laboratory over the last several years provide evidence that oxidized phospholipids, present in OxLDL and also in the membrane of apoptotic cells, represent one such ligand. These oxidized phospholipids, either in the lipid phase of OxLDL or becoming attached covalently to apoprotein B during LDL oxidation, have been shown to play a major role in the binding of OxLDL to CD36 and to SR-B1 expressed in transfected cells. The lipid and protein moieties compete with each other to some extent, indicating that they are binding to at least one common site. A monoclonal antibody selected because of its reactivity with OxLDL proved to be an antibody against oxidized phospholipids (but not native phospholipids). This antibody (EO6) blocked the uptake of OxLDL by CD36 and by SR-B1 in transfected cells by as much as 80%; it also inhibited macrophage phagocytosis of apoptotic cells by about 40%. Thus, the persistence of receptors for OxLDL during evolution is probably accounted for by their role in recognition of ligands on the surfaces of oxidatively damaged or apoptotic cells. This has important implications in biology generally and specifically in atherogenesis, because apoptosis is a prominent feature of late lesions.
Boullier
A
A
Department of Medicine, University of California, San Diego, La Jolla 92093, USA.
Bird
D A
DA
Chang
M K
MK
Dennis
E A
EA
Friedman
P
P
Gillotre-Taylor
K
K
Hörkkö
S
S
Palinski
W
W
Quehenberger
O
O
Shaw
P
P
Steinberg
D
D
Terpstra
V
V
Witztum
J L
JL
D000818:Animals; D017209:Apoptosis; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D018955:CD36 Antigens; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000502:physiology*; D008565:Membrane Proteins; D011971:Receptors, Immunologic / Q000502:physiology*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C099252:oxidized low density lipoprotein