Role of Monocyte Chemoattractant Protein-1 in Various Pathological Conditions

单核细胞趋化蛋白-1 （MCP-1）是单核细胞最有效的趋化因子之一，属于C-C趋化因子群。在本项目中，我们明确了MCP-1在大鼠各种病理状态中的关键作用。将重组大鼠MCP-1注入大鼠皮肤可诱导trpm -3阳性活化巨噬细胞浸润，而ed2阳性常驻巨噬细胞未积聚到注射部位。在肺肉芽肿大鼠模型中，我们证实了MCP-1在炎症早期的表达。一氧化氮合酶抑制剂显著抑制一氧化氮（NO）的产生，显著减少单核细胞/巨噬细胞的浸润，抑制MCP-1的产生。提示NO可诱导肺肉芽肿组织中MCP-1的表达。在胶原诱导的大鼠关节炎中，关节灌洗液中MCP-1浓度和关节组织中MCP-1 mRNA水平在免疫后2周均有明显变化。与对照组相比，注射抗大鼠MCP-1单克隆抗体可显著减少病变中渗出巨噬细胞的数量，使踝关节肿胀减轻约30%。这些结果表明MCP-1在单核细胞的募集和大鼠关节炎的发展中起着关键作用。在月牙形肾小球肾炎大鼠中，MCP-1 mRAN和蛋白与单核/巨噬细胞浸润肾小球呈平行关系。MCP-1 mRNA在抗肾小球基底膜抗体注射4天后在肾小球内表达强烈。用抗MCP-1抗体中和MCP-1后，第4天肾小球单核/巨噬细胞浸润数量减少34.7%，蛋白尿减少66.4%。这些数据表明MCP-1在单核细胞/巨噬细胞的肾小球积聚中起着至关重要的作用，浸润的单核细胞/巨噬细胞导致肾小球损伤和尿液中蛋白质排泄增加。少

Monocyte chemoattractant protein-1 (MCP-1) is one of the most potent chemoattractants for monocytes which belongs to the C-C chemokine group. In this project, we clarified the crucial role of MCP-1 in various pathological conditions in rats.1.Injection of recombinant rat MCP-1 into rat skin induced infiltration of TRPM-3-positive activated macrophages, whereas ED2-positive resident macrophages did not accumulate to the injection site.2.In rat models of pulmonary granulomatosis, we confirmed the expression of MCP-1 in the early phase of inflammation. Administration of nitric oxide synthase inhibitors significantly suppressed nitric oxide (NO) production and resulted in marked reduction monocyte/macrophage infiltration as well as in inhibition of MCP-1 production. These data indicate that NO may induce MCP-1 expression in lung granulomatosis.3.In collagen-induced rat arthritis, both MCP-1 concentration in the joint lavages and MCP-1 mRNA levels in the joint tissues at 2 weeks after the i … More mmunization of collagen. Injection of an anti-rat MCP-1 monoclonal antibody significantly decreased the number of exudate macrophages in the lesions and reduced the ankle swelling by about 30% compared with controls. These results suggest that MCP-1 plays a critical role in the recruitment of monocytes and in the development of rat arthritis.4.IN crescentic glomeruionephritis in rats, MCP-1 mRAN and proein are paralleled with the infiltration of monocyte/macrophages into glomeruli. MCP-1 mRNA was expressed intensely in the glomeruli 4days after the anti-glomerular basement membrane antibody injection. When MCP-1 was neutralized with anti-MCP-1 antibody administration, the number of monocyte/macrophage infiltrating in the glomeruli decreased by 34.7% and proteinuria by 66.4% at day 4. These data suggest that MCP-1 plays a crucial role in the glomerular accumulation of monocyte/macrophages and that the infiltrating monocyte/macrophages cause glomerular injury and increased excretion of protein in the urine. Less