Wada T, Yokoyama H, Furuichi K, Kobayashi K I, Harada K, Naruto M, Su S B, Akiyama M, Mukaida N, Matsushima K
First Department of Internal Medicine, School of Medicine, Kanazawa University, Japan.
FASEB J. 1996 Oct;10(12):1418-25.
We investigated the pathophysiological role of a potent macrophage (M(phi)) chemotactic cytokine (chemokine), monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 (MCAF/MCP-1), in an animal model of crescentic glomerulonephritis. Administration of a small dose of nephrotoxic sera induced severe proliferative and necrotizing glomerulonephritis, with crescentic formation in the early phase and glomerulosclerosis in the later phase, in Wistar-Kyoto rats. MCAF/MCP-1 protein was detected immunohistochemically in glomeruli, vascular endothelial cells, and tubular epithelial cells in the early phase of injured kidney tissues but not in normal ones. Anti-MCAF/MCP-1 antibodies decreased the number of M(phi) in glomeruli, and prevented crescentic formation and the fusion of epithelial cell foot process in nephritic rats, thereby decreasing the excreted amounts of protein to normal levels on days 3 and 6. Furthermore, anti-MCAF/MCP-1 antibodies remarkably reduced glomerulosclerosis and improved renal dysfunction as well as proteinuria in the later phase (56 days). These results indicate that MCAF/MCP-1 essentially participates in the impairment of renal functions associated with crescentic glomerulonephritis by recruiting and activating M(phi).
我们在新月体性肾小球肾炎动物模型中研究了一种强效巨噬细胞（M(phi)）趋化细胞因子（趋化因子）——单核细胞趋化和激活因子/单核细胞趋化蛋白-1（MCAF/MCP-1）的病理生理作用。给Wistar-Kyoto大鼠注射小剂量肾毒性血清可诱导严重的增殖性和坏死性肾小球肾炎，早期出现新月体形成，后期出现肾小球硬化。在受损肾组织早期，通过免疫组织化学方法可在肾小球、血管内皮细胞和肾小管上皮细胞中检测到MCAF/MCP-1蛋白，而在正常组织中未检测到。抗MCAF/MCP-1抗体可减少肾小球中M(phi)的数量，并防止肾炎大鼠出现新月体形成和上皮细胞足突融合，从而在第3天和第6天将蛋白排泄量降至正常水平。此外，抗MCAF/MCP-1抗体在后期（56天）可显著减轻肾小球硬化，改善肾功能障碍及蛋白尿。这些结果表明，MCAF/MCP-1通过募集和激活M(phi)，本质上参与了与新月体性肾小球肾炎相关的肾功能损害。
