Badie B, Schartner J M
Department of Neurological Surgery, University of Wisconsin School of Medicine, Madison 53792-3232, USA.
Neurosurgery. 2000 Apr;46(4):957-61; discussion 961-2. doi: 10.1097/00006123-200004000-00035.
Although microglia have been suggested to be a component of the inflammatory reaction to tumors of the central nervous system, their role in glioma biology remains unknown. One obstacle to studying the function of microglia is the inability to effectively separate them from macrophages. Because flow cytometry can effectively discern immune cells with similar surface antigens, we evaluated its role in characterizing the mononuclear cell infiltration in experimental gliomas.
Freshly prepared rat C6, 9L, and RG-2 tumor specimens were labeled ex vivo with monoclonal antibodies against CD11b/c, CD45, and CD8a antigens and analyzed by flow cytometry. The extent of microglia (CD11b/c(high), CD45(low)), macrophage (CD11b/c(high), CD45(high)), and lymphocyte (CD11b/c(negative), CD45(high)) infiltration into tumors, tumor periphery, and contralateral tumor-free hemispheres was measured for each glioma type.
Microglia, which accounted for 13 to 34% of viable cells, were distributed throughout the central nervous system and were present in the tumors, tumor periphery, and contralateral tumor-free hemispheres. In contrast, macrophages were less prominent within the tumors and tumor periphery (4.2-12%) and were scarce in the contralateral tumor-free hemispheres (0.9-1.1%). Among the tumor types, RG-2 gliomas had the least microglia/macrophage infiltration. The frequency and the distribution pattern of lymphocytes also varied among tumor models. Whereas lymphocytes accounted for more than one-third of the cells in C6 and 9L tumors, they represented only 1% of cells in RG-2 gliomas.
More abundant than macrophages and scattered throughout the central nervous system, microglia account for a significant component of the inflammatory response to experimental gliomas. A better understanding of microglial function in gliomas may be important in the development of immunotherapy strategies.
虽然已有研究表明小胶质细胞是中枢神经系统肿瘤炎症反应的一个组成部分，但其在胶质瘤生物学中的作用仍不清楚。研究小胶质细胞功能的一个障碍是无法有效地将它们与巨噬细胞分离。由于流式细胞术能够有效区分具有相似表面抗原的免疫细胞，我们评估了其在表征实验性胶质瘤中单核细胞浸润情况方面的作用。
将新鲜制备的大鼠C6、9L和RG - 2肿瘤标本在体外用抗CD11b/c、CD45和CD8a抗原的单克隆抗体进行标记，然后通过流式细胞术进行分析。测量每种胶质瘤类型中，小胶质细胞（CD11b/c(高)，CD45(低)）、巨噬细胞（CD11b/c(高)，CD45(高)）和淋巴细胞（CD11b/c(阴性)，CD45(高)）浸润到肿瘤、肿瘤周边和对侧无肿瘤半球的程度。
小胶质细胞占活细胞的13%至34%，分布于整个中枢神经系统，在肿瘤、肿瘤周边和对侧无肿瘤半球均有存在。相比之下，巨噬细胞在肿瘤和肿瘤周边不那么突出（4.2 - 12%），在对侧无肿瘤半球中很少见（0.9 - 1.1%）。在肿瘤类型中，RG - 2胶质瘤的小胶质细胞/巨噬细胞浸润最少。淋巴细胞的频率和分布模式在不同肿瘤模型中也有所不同。虽然淋巴细胞在C6和9L肿瘤中占细胞总数的三分之一以上，但在RG - 2胶质瘤中仅占细胞总数的1%。
小胶质细胞比巨噬细胞更丰富，且散布于整个中枢神经系统，是实验性胶质瘤炎症反应的重要组成部分。更好地了解小胶质细胞在胶质瘤中的功能可能对免疫治疗策略的开发具有重要意义。
