title: The class A scavenger receptor binds to proteoglycans and mediates adhesion of macrophages to the extracellular matrix.
abstract: The class A scavenger receptor (SR-A) binds modified lipoproteins and has been implicated in cholesterol ester deposition in macrophages. The SR-A also contributes to cellular adhesion. Using SR-A(+/+) and SR-A(-)/- murine macrophages, we found SR-A expression important for both divalent cation-dependent and -independent adhesion of macrophages to the human smooth muscle cell extracellular matrix. The SR-A mediated 65 and 85% of macrophage adhesion to the extracellular matrix in the presence and absence of serum, respectively. When EDTA was added to chelate divalent cations, the SR-A mediated 90 and 95% of the macrophage adhesion without and with serum, respectively. SR-A-mediated adhesion to the extracellular matrix was prevented by fucoidin, an SR-A antagonist. Biglycan and decorin, proteoglycans of the extracellular matrix, were identified as SR-A ligands. Compared with control cells, Chinese hamster ovary cells expressing the SR-A showed 5- and 6-fold greater cell association (binding and internalization) of (125)I-decorin and -biglycan, respectively. In competition studies, unlabeled proteoglycan or fucoidin competed for binding of (125)I-labeled decorin and -biglycan, and biglycan and decorin competed for the SR-A-mediated cell association and degradation of (125)I-labeled acetylated LDL, a well characterized ligand for the SR-A. These results suggest that the SR-A could contribute to the adhesion of macrophages to the extracellular matrix of atherosclerotic plaques.
authors.affiliation: Gladstone Institutes of Cardiovascular Disease and Neurological Disease, Cardiovascular Research Institute, Department of Pathology, University of California, San Francisco, California 94143, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Santiago-García
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Robert E
authors.initials: RE
authors.lastname: Pitas
mesh_terms: D000818:Animals; D058578:Biglycan; D001667:Binding, Competitive; D018955:CD36 Antigens / Q000378:metabolism*; D016466:CHO Cells; D002412:Cations; D002417:Cattle; D002448:Cell Adhesion; D006224:Cricetinae; D058575:Decorin; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins; D006801:Humans; D008024:Ligands; D008074:Lipoproteins / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011134:Polysaccharides / Q000378:metabolism; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism*; D051117:Scavenger Receptors, Class A; D013997:Time Factors; D014357:Trypsin / Q000494:pharmacology
chemical_list: C546884:BGN protein, human; C546885:Bgn protein, mouse; D058578:Biglycan; D018955:CD36 Antigens; D002412:Cations; C546878:DCN protein, human; C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D008024:Ligands; D008074:Lipoproteins; D008077:Lipoproteins, LDL; C495140:Msr1 protein, mouse; D011134:Polysaccharides; D011509:Proteoglycans; D051117:Scavenger Receptors, Class A; C007789:fucoidan; D014357:Trypsin