Becher B, Antel J P
Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Glia. 1996 Sep;18(1):1-10. doi: 10.1002/(SICI)1098-1136(199609)18:1<1::AID-GLIA1>3.0.CO;2-6.
Microglial cells are resident cells of the CNS and are implicated as regulators and effectors of immune responses which occur within this compartment. The precise role of parenchymal microglia remains speculative because distinctions between these cells, perivascular "microglia," and blood-derived monocytes/macrophages are not well defined. The current study describes the phenotype and function of microglia immediately upon isolation from the non-inflamed adult human CNS and the phenotypic changes which occur in these cells when maintained in tissue culture. We find that the characteristic phenotype of immediately ex vivo parenchymal microglia (CD11c+/CD45low/CD14) corresponds to that found in situ in the "normal" human brain. The phenotype differs from that of perivascular "microglia" in situ and PBDM (both CD45hi/CD14++). The immediately ex vivo microglia express B7-2 and HLA class II molecules and can support alloantigen-induced proliferation by CD4+ T cells freshly isolated from peripheral blood. Following in vitro culture, the cells are characterized by a bipolar morphology, continued lower levels of CD45 expression compared to PBDM, and slight upregulation of B7-1 and HLA-DR antigen expression. CD14 becomes expressed at high levels on the cells, suggesting that CD14 can serve as an apparent marker of microglia activation which is not based on changes in morphology or APC capacity. Further, treatment of the cells with IFN-gamma and LPS causes further upregulation of HLA-DR and clear expression of B7-1 molecules on the surface. The capacity to characterize phenotypic and functional properties of microglia before and after activation provides an opportunity to determine means to manipulate the immune regulatory and effector properties of this cell type.
小胶质细胞是中枢神经系统的常驻细胞，被认为是该区域内免疫反应的调节者和效应器。实质小胶质细胞的确切作用仍具有推测性，因为这些细胞、血管周围“小胶质细胞”和血液来源的单核细胞/巨噬细胞之间的区别尚未明确界定。本研究描述了从小胶质细胞从非炎症的成年人类中枢神经系统中分离出来后立即呈现的表型和功能，以及这些细胞在组织培养中维持时发生的表型变化。我们发现，刚离体的实质小胶质细胞（CD11c+/CD45low/CD14）的特征性表型与“正常”人类大脑中原位发现的表型一致。该表型与原位血管周围“小胶质细胞”和外周血来源的巨噬细胞（两者均为CD45hi/CD14++）的表型不同。刚离体的小胶质细胞表达B7-2和HLA II类分子，并能支持从外周血新分离的CD4+ T细胞的同种异体抗原诱导的增殖。体外培养后，这些细胞的特征是具有双极形态，与外周血来源的巨噬细胞相比，CD45表达水平持续较低，B7-1和HLA-DR抗原表达略有上调。CD14在这些细胞上高水平表达，这表明CD14可作为小胶质细胞激活的明显标志物，其并非基于形态学或抗原呈递细胞能力的变化。此外，用干扰素-γ和脂多糖处理这些细胞会导致HLA-DR进一步上调以及B7-1分子在表面清晰表达。能够表征激活前后小胶质细胞的表型和功能特性，为确定操纵这种细胞类型的免疫调节和效应特性的方法提供了机会。
