Santiago-García Juan, Kodama Tatsuhiko, Pitas Robert E
Gladstone Institutes of Cardiovascular Disease and Neurological Disease, Cardiovascular Research Institute, Department of Pathology, University of California, San Francisco, California 94143, USA.
J Biol Chem. 2003 Feb 28;278(9):6942-6. doi: 10.1074/jbc.M208358200. Epub 2002 Dec 17.
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.
A类清道夫受体（SR-A）可结合修饰的脂蛋白，并与巨噬细胞中胆固醇酯的沉积有关。SR-A还参与细胞黏附。利用SR-A(+/+)和SR-A(-)/-小鼠巨噬细胞，我们发现SR-A的表达对于巨噬细胞与人类平滑肌细胞细胞外基质的二价阳离子依赖性和非依赖性黏附均很重要。在有血清和无血清的情况下，SR-A分别介导了65%和85%的巨噬细胞与细胞外基质的黏附。当加入乙二胺四乙酸（EDTA）螯合二价阳离子时，SR-A在无血清和有血清的情况下分别介导了90%和95%的巨噬细胞黏附。岩藻依聚糖（一种SR-A拮抗剂）可阻止SR-A介导的与细胞外基质的黏附。细胞外基质的蛋白聚糖双糖链蛋白聚糖和饰胶蛋白聚糖被鉴定为SR-A配体。与对照细胞相比，表达SR-A的中国仓鼠卵巢细胞对(¹²⁵)I-饰胶蛋白聚糖和-双糖链蛋白聚糖的细胞结合（结合和内化）分别增加了5倍和6倍。在竞争研究中，未标记的蛋白聚糖或岩藻依聚糖竞争(¹²⁵)I标记的饰胶蛋白聚糖和-双糖链蛋白聚糖的结合，双糖链蛋白聚糖和饰胶蛋白聚糖竞争SR-A介导的(¹²⁵)I标记的乙酰化低密度脂蛋白（一种已明确的SR-A配体）的细胞结合和降解。这些结果表明，SR-A可能有助于巨噬细胞与动脉粥样硬化斑块细胞外基质的黏附。
