TURNOVER OF RESIDENT MICROGLIA IN THE NORMAL ADULT-MOUSE BRAIN
TURNOVER OF RESIDENT MICROGLIA IN THE NORMAL ADULT-MOUSE BRAIN
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DOI：
10.1016/0306-4522(92)90500-2
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发表时间：
1992-05-01
期刊：
影响因子：
3.3
通讯作者：
GORDON, S
中科院分区：
文献类型：
--
作者：
LAWSON, LJ;PERRY, VH;GORDON, S
我们进行了这项研究，以确定是否小胶质细胞，中枢神经系统的居民巨噬细胞，在稳态翻转。脑巨噬细胞的周转将支持中枢神经系统感染的“特洛伊木马”假说，因为替代细胞的一个来源是循环单核细胞池。我们结合免疫组化检测F4/80，一个特定的巨噬细胞标志物，[H-3]胸苷掺入和放射自显影在正常成年小鼠。我们可以检测到同位素给药后灌注60分钟的小鼠脑中的双标记细胞。这种细胞数量很少，随机分散在整个大脑中，具有典型的常驻细胞的形态。该存活时间的标记指数为0.052 +/-0.003%。因此，常驻的小胶质细胞可以在原位合成DNA。经过较长的存活时间后，我们检测到大量的双标记细胞。具有常驻形态、有丝分裂像、成对紧密贴壁（子）细胞和圆形巨噬细胞样形态的F4/80+细胞均显示银标记。同位素给药后24小时标记指数为0.192 +/-0.052%。从形态学证据和不同存活时间标记指数的比较中，我们得出结论：（i）驻留的小胶质细胞可以合成DNA并继续原位分裂;（ii）细胞通过完整的血脑屏障从循环单核细胞库中募集并迅速分化为驻留的小胶质细胞。我们估计这两个过程对常驻小胶质细胞稳态周转的贡献几乎相同。
We undertook this study to determine whether the microglia, the resident macrophages of the central nervous system, turn over in the steady-state. The turnover of brain macrophages would lend support to the "Trojan Horse" hypothesis of central nervous system infection, since one origin of replacement cells is the circulating monocyte pool. We combined the immunohistochemical detection of F4/80, a specific macrophage marker, with [H-3]thymidine incorporation and autoradiography in normal adult mice. We could detect double-labelled cells in the brains of mice perfused 60 min after isotope administration. Such cells were few in number, randomly scattered throughout the brain and had the morphology of typical resident cells. The labelling index at this survival time was 0.052 +/- 0.003%. Thus resident microglia can synthesise DNA in situ. After longer survival times, we detected larger numbers of double-labelled cells. F4/80+ cells with resident morphology, mitotic figures, pairs of closely apposed (daughter) cells and cells with rounded macrophage-like morphology, all exhibited silver labelling. Twenty-four hours after isotope administration the labelling index was 0.192 +/- 0.052%.From morphologic evidence and comparison of labelling indices at different survival times, we concluded that: (i) resident microglia can synthesise DNA and go on to divide in situ; (ii) cells are recruited from the circulating monocyte pool through an intact blood-brain barrier and rapidly differentiate into resident microglia. We estimate that the two processes contribute almost equally to the steady-state turnover of resident microglia.