Mukaida N, Harada A, Matsushima K
Department of Molecular Pharmacology, Cancer Research Institute, Kanazawa University, Japan.
Cytokine Growth Factor Rev. 1998 Mar;9(1):9-23. doi: 10.1016/s1359-6101(97)00022-1.
Leukocyte infiltration is a hallmark of inflammation. Knowledge on molecular mechanisms of leukocyte infiltration has advanced rapidly due to the recent elucidation of structures and functions of adhesion molecules and chemokines. Since the discovery of interleukin-8 (IL-8), a prototype of CXC chemokines, in 1987 and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 (MCAF/MCP-1), a prototype of chemotactic cytokines (CC) chemokines, in 1989, more than 30 members of chemokines have been identified so far. Evidence is accumulating that these chemokines exert overlapping but distinct actions on specific types of leukocytes in vitro through interacting with their specific G-protein-coupled receptors with seven transmembrane domains. However, redundancy at receptor levels has frequently hindered the clarification on the precise physiological or pathophysiological roles of chemokines. Here, we describe the pathophysiological roles of IL-8 and MCAF/MCP-1 in several animal models of neutrophil- and macrophage-mediated inflammation, respectively, by focusing on our recent work using neutralizing antibodies to these chemokines. We discuss further potential roles of these chemokines in T-lymphocyte-mediated immune responses.
白细胞浸润是炎症的一个标志。由于最近对黏附分子和趋化因子的结构与功能有了阐明,关于白细胞浸润分子机制的知识迅速发展。自1987年发现白细胞介素8(IL-8)(CXC趋化因子的原型)以及1989年发现单核细胞趋化和激活因子/单核细胞趋化蛋白-1(MCAF/MCP-1)(趋化因子(CC)趋化因子的原型)以来,迄今已鉴定出30多种趋化因子。越来越多的证据表明,这些趋化因子通过与具有七个跨膜结构域的特定G蛋白偶联受体相互作用,在体外对特定类型的白细胞发挥重叠但不同的作用。然而,受体水平的冗余常常阻碍对趋化因子精确生理或病理生理作用的阐明。在此,我们分别通过关注我们最近使用针对这些趋化因子的中和抗体所开展的工作,来描述IL-8和MCAF/MCP-1在中性粒细胞和巨噬细胞介导的炎症的几种动物模型中的病理生理作用。我们还讨论了这些趋化因子在T淋巴细胞介导的免疫反应中的进一步潜在作用。