Bennett Jami L, Elhofy Adam, Canto Mauro C Dal, Tani Mari, Ransohoff Richard M, Karpus William J
Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
J Neurovirol. 2003 Dec;9(6):623-36. doi: 10.1080/13550280390247551.
CCL2 is a member of the CC chemokine family that mediates the migration and recruitment of monocytes and T cells and has been identified in the central nervous system (CNS) during several neuroinflammatory diseases. In order to examine the biological effect of constitutive CCL2 expression in the CNS, the authors engineered a mouse that expressed CCL2 in the CNS under control of the human glial fibrillary acidic protein (hGFAP) promoter. The results demonstrated that transgenic expression of CCL2 in the CNS resulted in diffuse CNS monocyte infiltration and accumulation. Transgenic CCL2 expression did not alter normal development, differentiation, or function of T cells. There was no evidence of overt CNS disease or other pathologic phenotype when mice were left unchallenged with antigen or uninfected. However, when CCL2 transgenic mice were given a peripheral challenge of lipopolysaccharide (LPS), an inflammatory infiltrate with organized perivascular lesions developed. Infection of the transgenic mice with Theiler's murine encephalomyelitis virus (TMEV) resulted in accelerated onset and increased severity of clinical and histological disease. These results suggest that CCL2 expression in the CNS is a major pathogenic factor that drives macrophage accumulation in the development of CNS inflammatory disease.
CCL2是CC趋化因子家族的一员，可介导单核细胞和T细胞的迁移与募集，并且在几种神经炎症性疾病期间已在中枢神经系统（CNS）中被鉴定出来。为了研究CNS中组成性CCL2表达的生物学效应，作者构建了一种小鼠，该小鼠在人胶质纤维酸性蛋白（hGFAP）启动子的控制下在CNS中表达CCL2。结果表明，CNS中CCL2的转基因表达导致弥漫性CNS单核细胞浸润和积聚。转基因CCL2表达并未改变T细胞的正常发育、分化或功能。当小鼠不接受抗原刺激或未被感染时，没有明显的CNS疾病或其他病理表型的证据。然而，当给CCL2转基因小鼠进行外周脂多糖（LPS）刺激时，会出现伴有有组织的血管周围病变的炎性浸润。用泰勒氏鼠脑脊髓炎病毒（TMEV）感染转基因小鼠会导致临床和组织学疾病的发病加速且严重程度增加。这些结果表明，CNS中CCL2的表达是在CNS炎性疾病发展过程中驱动巨噬细胞积聚的主要致病因素。
