Predominant phagocytic activity of resident microglia over hematogenous macrophages following transient focal cerebral ischemia:: An investigation using green fluorescent protein transgenic bone marrow chimeric mice
Predominant phagocytic activity of resident microglia over hematogenous macrophages following transient focal cerebral ischemia:: An investigation using green fluorescent protein transgenic bone marrow chimeric mice
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DOI：
10.1016/j.expneurol.2005.08.004
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发表时间：
2005-12-01
影响因子：
5.3
通讯作者：
Kiefer, R
中科院分区：
文献类型：
--
作者：
Schilling, M;Besselmann, M;Kiefer, R
已知活化的小胶质细胞和造血巨噬细胞参与脑缺血后梗死的发展。传统上，造血巨噬细胞被认为是清除缺血细胞碎片的主要细胞。然而，吞噬作用也是活化小胶质细胞的一个众所周知的特性。由于缺乏可鉴别的细胞标记，吞噬细胞的细胞起源和这两种细胞吞噬的时间过程在很大程度上是未知的。本研究采用绿色荧光蛋白（GFP）转基因骨髓嵌合小鼠和经甲基丙烯酸甲酯包埋后的半薄连续切片，详细解剖了短暂局灶性脑缺血30min后，鉴定活化的常驻小胶质细胞和浸润性造血巨噬细胞在吞噬神经元细胞碎片中的比例。在再灌注后第1天，我们发现缺血组织中的神经元迅速减少，在第7天达到最低数量。常驻gfp阴性的小胶质细胞在第一天迅速被激活，并开始吞噬神经元物质。相比之下，不早于第4天在缺血区观察到含有神经元细胞碎片的造血巨噬细胞。定量分析显示，局部来源的吞噬细胞数量在第2天达到最大值，血源性巨噬细胞在第4天达到最大值。梗死区域的大部分吞噬细胞来源于局部的小胶质细胞，先于并主导着血源性吞噬细胞。这种招募揭示了局部防御机制对组织清除的显著优势，而不是缺血损伤后来自血液的免疫细胞。(c) 2005爱思唯尔公司版权所有。
Activated microglia and hematogenous macrophages are known to be involved in infarct development after cerebral ischemia. Traditionally, hematogenic macrophages are thought to be the primary cells to remove the ischemic cell debris. However, phagocytosis is a well known property also of activated microglia. Due to a lack of discriminating cellular markers, the cellular origin of phagocytes and the temporal course of phagocytosis by these two cell types are largely unknown. In this study, we used green fluorescent protein (GFP) transgenic bone marrow chimeric mice and semithin serial sections after methyl methacrylate embedding of the brains to dissect in detail the proportion of identified activated resident microglial cells and infiltrating hematogenous macrophages in phagocytosing neuronal cell debris after 30 min of transient focal cerebral ischemia. Already at day one after reperfusion, we found a rapid decrease of neurons in the ischemic tissue reaching minimum numbers at day seven. Resident GFP-negative microglial cells rapidly became activated at day one and started to phagocytose neuronal material. By contrast, hematogenous macrophages incorporating neuronal cell debris were observed in the ischemic area not earlier than on day four. Quantitative analysis showed maximum numbers of phagocytes of local origin within 2 days and of bloodborne macrophages on day four. The majority of phagocytes in the infarct area were derived from local microglia, preceding and predominating over phagocytes of hematogenous origin. This recruitment reveals a remarkable predominance of local defense mechanisms for tissue clearance over immune cells arriving from the blood after ischemic damage. (c) 2005 Elsevier Inc. All rights reserved.