Simpson J E, Newcombe J, Cuzner M L, Woodroofe M N
Department of Biomedical Sciences, Sheffield Hallam University, City Campus, South Yorkshire, UK.
J Neuroimmunol. 1998 Apr 15;84(2):238-49. doi: 10.1016/s0165-5728(97)00208-7.
Beta-chemokines induce the directional migration of monocytes and T lymphocytes and are thus associated with chronic inflammation. Using immunocytochemistry and in situ hybridisation (ISH) techniques, we have examined the expression of the beta-chemokines monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated upon activation, normal T cell expressed and secreted) in post-mortem human brain from multiple sclerosis (MS) cases, at different stages of lesion development. In actively demyelinating MS plaques RANTES expression was restricted to the blood vessel endothelium, perivascular cells and surrounding astrocytes, suggesting a role in the recruitment of inflammatory cells from the circulation. MCP-1 was expressed by astrocytes and macrophages within acute MS lesions, but was restricted to reactive astrocytes in the parenchyma surrounding the lesion. MIP-1alpha was expressed by astrocytes and macrophages within the plaque, while MIP-1beta was expressed by macrophages and microglia within the lesion, and by microglia in surrounding white matter. Glial cells may be stimulated to produce chemokines and continue the local inflammatory response by forming chemotactic gradients to attract T cells and mononuclear phagocytes from the circulation and surrounding tissue.
β-趋化因子可诱导单核细胞和T淋巴细胞的定向迁移，因此与慢性炎症相关。我们运用免疫细胞化学和原位杂交（ISH）技术，检测了多发性硬化症（MS）患者尸检人脑在病变发展不同阶段中β-趋化因子单核细胞趋化蛋白-1（MCP-1）、巨噬细胞炎性蛋白（MIP）-1α、MIP-1β和调节激活正常T细胞表达和分泌因子（RANTES）的表达情况。在正在进行脱髓鞘的MS斑块中，RANTES的表达局限于血管内皮细胞、血管周围细胞及周围的星形胶质细胞，提示其在从循环中募集炎性细胞方面发挥作用。MCP-1在急性MS病变中的星形胶质细胞和巨噬细胞中表达，但在病变周围实质中仅限于反应性星形胶质细胞表达。MIP-1α在斑块内的星形胶质细胞和巨噬细胞中表达，而MIP-1β在病变内的巨噬细胞和小胶质细胞以及周围白质的小胶质细胞中表达。胶质细胞可能受到刺激产生趋化因子，并通过形成趋化梯度吸引循环和周围组织中的T细胞和单核吞噬细胞，从而持续局部炎症反应。
