The 94- to 97-kDa mouse macrophage membrane protein that recognizes oxidized low density lipoprotein and phosphatidylserine-rich liposomes is identical to macrosialin, the mouse homologue of human CD68.
We have previously reported the partial purification of a 94- to 97-kDa plasma membrane protein from mouse peritoneal macrophages that binds oxidatively modified low density lipoprotein (OxLDL) and phosphatidylserine-rich liposomes. We have now identified that protein as macrosialin, a previously cloned macrophage-restricted membrane protein in the lysosomal-associated membrane protein family (mouse homologue of human CD68). Early in the course of purification of the 94- to 97-kDa protein, a new OxLDL-binding band at 190-200 kDa appeared and copurified with the 94- to 97-kDa protein. The HPLC pattern of tryptic peptides from this higher molecular mass ligand-binding band closely matched that derived from the 94- to 97-kDa band. Specifically, the same three macrosialin-derived tryptic peptides (9, 9, and 15 residues) were present in the purified 94- to 97-kDa band and in the 190- to 200-kDa band and antisera raised against peptide sequences in macrosialin recognized both bands. An antiserum against macrosialin precipitated most of the 94- to 97-kDa OxLDL-binding material. We conclude that the binding of OxLDL to mouse macrophage membranes is in part attributable to macrosialin. Our previous studies show that OxLDL competes with oxidized red blood cells and with apoptotic thymocytes for binding to mouse peritoneal macrophages. Whether macrosialin plays a role in recognition of OxLDL and oxidatively damaged cells by intact macrophages remains uncertain.
Ramprasad
M P
MP
Department of Medicine, University of California, La Jolla 92093, USA.
Fischer
W
W
Witztum
J L
JL
Sambrano
G R
GR
Quehenberger
O
O
Steinberg
D
D
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000737:chemistry* / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D008024:Ligands; D008077:Lipoproteins, LDL / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000737:chemistry*; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010718:Phosphatidylserines / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017421:Sequence Analysis; D013347:Subcellular Fractions; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D008024:Ligands; D008077:Lipoproteins, LDL; D008081:Liposomes; D008562:Membrane Glycoproteins; D010718:Phosphatidylserines; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C081026:CD68 protein, mouse