Saishoji T, Higashi T, Ikeda K, Sano H, Jinnouchi Y, Ogawa M, Horiuchi S
Department of Biochemistry, Kumamoto University School of Medicine, Japan.
Biochem Biophys Res Commun. 1995 Dec 5;217(1):278-85. doi: 10.1006/bbrc.1995.2775.
The effects of advanced glycation end products (AGE) on the plasminogen activator (PA) activity were investigated with murine macrophage cell line RAW 264.7 cells. AGE-bovine serum albumin (BSA) showed a dose-dependent induction for the urokinase-type PA (uPA) activity. The uPA induction by AGE-BSA was effectively suppressed by the antibody against granulocyte-macrophage colony-stimulating factor (GM-CSF). The uPA activity of these cells was also induced by ligands for the macrophage scavenger receptor (MSR). These data provide evidence that AGE-BSA stimulates the uPA activity via GM-CSF through MSR in RAW cells. These findings, taken together with a recent demonstration of endocytic uptake of AGE-proteins by MSR in vitro and the presence of AGE-proteins in atherosclerotic lesions, strongly suggest that the uPA induction by AGE-proteins via MSR plays an important role in human atherogenesis.
利用小鼠巨噬细胞系RAW 264.7细胞研究了晚期糖基化终产物（AGE）对纤溶酶原激活剂（PA）活性的影响。AGE-牛血清白蛋白（BSA）对尿激酶型PA（uPA）活性呈剂量依赖性诱导作用。抗粒细胞-巨噬细胞集落刺激因子（GM-CSF）抗体可有效抑制AGE-BSA对uPA的诱导作用。巨噬细胞清道夫受体（MSR）的配体也可诱导这些细胞的uPA活性。这些数据证明，在RAW细胞中，AGE-BSA通过MSR经GM-CSF刺激uPA活性。这些发现，连同最近在体外证明MSR对AGE蛋白的内吞摄取以及动脉粥样硬化病变中存在AGE蛋白，强烈表明AGE蛋白经MSR诱导uPA在人类动脉粥样硬化形成中起重要作用。
