Classical activation of microglia in CD200-deficient mice is a consequence of blood brain barrier permeability and infiltration of peripheral cells
Classical activation of microglia in CD200-deficient mice is a consequence of blood brain barrier permeability and infiltration of peripheral cells
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DOI：
10.1016/j.bbi.2013.07.174
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发表时间：
2013-11-01
影响因子：
15.1
通讯作者：
Lynch, Marina A.
中科院分区：
文献类型：
--
作者：
Denieffe, Stephanie;Kelly, Ronan J.;Lynch, Marina A.
在几种细胞类型上表达的CD 200与在髓系细胞上表达的其受体CD 200 R之间的相互作用已被证明是在包括结肠炎和关节炎的几种病症中调节巨噬细胞功能中的炎症的重要因素。最近，它对小胶质细胞活化的调节作用已被确定，并且CD 200缺陷与伴随炎性细胞因子产生增加的小胶质细胞活化增加有关。从CD 200缺陷型小鼠制备的神经胶质细胞对刺激物如脂多糖（LPS）的反应明显大于从野生型小鼠制备的细胞的反应，并且与此一致的是最近的观察结果，即在从CD 200缺陷型小鼠制备的小神经胶质细胞中Toll样受体（TLR）4的表达和通过NP κ B的信号传导增加。在这里，我们表明，从CD 200缺陷小鼠的神经胶质细胞也更响应于干扰素γ（IFN γ），触发经典的小胶质细胞激活。我们研究了体内CD 200缺乏的影响，并报告了几种小胶质细胞活化标志物的表达增加，包括肿瘤坏死因子（TNE）-α，这是经典活化小胶质细胞的标志。这些变化伴随着IFN γ的增加，证据表明这是由浸润细胞包括T细胞和巨噬细胞产生的。我们提出，这些细胞进入大脑的CD 200缺陷小鼠的血脑屏障（BBB）的通透性增加的结果，并通过增加表达的趋化因子，单核细胞趋化蛋白-1（MCP-1），IFN γ诱导的蛋白-10（IP-10）和RANTES的浸润是辅助。这可能对BBB通透性受损的神经退行性疾病有影响。(C)2013 Elsevier Inc. All rights reserved.
The interaction between CD200, expressed on several cell types, and its receptor CD200R, expressed on cells of the myeloid lineage, has been shown to be an important factor in modulating inflammation in macrophage function in several conditions including colitis and arthritis. More recently its modulatory effect on microglial activation has been identified and CD200-deficiency has been associated with increased microglial activation accompanied by increased production of inflammatory cytokines. The response of glia prepared from CD200-deficient mice to stimuli like lipopolysaccharide (LPS) is markedly greater than the response of cells prepared from wildtype mice and, consistent with this, is the recent observation that expression of Toll-like receptor (TLR)4 and signalling through NP kappa B are increased in microglia prepared from CD200-deficient mice. Here we show that glia from CD200-deficient mice are also more responsive to interferon-gamma (IFN gamma) which triggers classical activation of microglia. We investigated the effects of CD200-deficiency in vivo and report that there is an increase in expression of several markers of microglial activation including tumor necrosis factor (TNE)-alpha, which is a hallmark of classically-activated microglia. These changes are accompanied by increased IFN gamma, and the evidence suggests that this is produced by infiltrating cells including T cells and macrophages. We propose that these cells enter the brain as a consequence of increased blood brain barrier (BBB) permeability in CD200-deficient mice and that infiltration is assisted by increased expression of the chemokines, monocyte chemotactic protein-1 (MCP-1), IFN gamma-induced protein-10 (IP-10) and RANTES. This may have implications in neurodegenerative diseases where BBB permeability is compromised. (C) 2013 Elsevier Inc. All rights reserved.