Dual role of CD38 in microglial activation and activation-induced cell death.
Dual role of CD38 in microglial activation and activation-induced cell death.
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DOI：
10.4049/jimmunol.181.1.92
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发表时间：
2008-07-01
期刊：
影响因子：
--
通讯作者：
Stein R
中科院分区：
文献类型：
--
作者：
Mayo L;Jacob-Hirsch J;Amariglio N;Rechavi G;Moutin MJ;Lund FE;Stein R
小胶质细胞是中枢神经系统的常驻免疫细胞，通常是静止的，但在感染或损伤后被激活。然后它们的性质发生变化，并促进修复和损坏过程。小胶质细胞活化的程度部分地通过活化诱导的细胞死亡（AICD）来调节。虽然小胶质细胞AICD机制的许多凋亡方面已经阐明，很少有人知道的激活步骤和死亡过程之间的联系。利用小鼠原代小胶质细胞培养物，我们发现胞外酶CD 38通过其钙动员代谢物环ADP核糖（cADPR）有助于促进小胶质细胞活化和LPS + IFNγ（LPS/IFNγ）诱导的AICD，表明CD 38连接这两个过程。因此，LPS/IFNγ处理增加了原代小胶质细胞中CD 38的表达和活性以及细胞内钙浓度（[Ca 2 +]i）。此外，CD 38缺陷或用cADPR拮抗剂处理赋予了对LPS/IFNγ诱导的AICD的部分抗性，并且还降低了[Ca 2 +]i。CD 38缺乏或cADPR拮抗剂处理可减弱小胶质细胞活化，表现为诱导的一氧化氮合酶-2 mRNA表达和NO产生，TNFα和IL-12 p40的分泌和mRNA表达，以及IL-6 mRNA表达。观察到的CD 38对小胶质细胞活化的影响可能是通过cADPR依赖性的[Ca 2 +]i增加介导的，并且通过调节NO产生对AICD的影响。因此，我们的研究结果表明，CD 38显着影响激活的小胶质细胞的数量和功能的调节，在大脑中的损伤和修复过程的重要后果。
Microglia, the resident immune cells of the central nervous system, are normally quiescent but become activated after infection or injury. Their properties then change, and they promote both repair and damage processes. The extent of microglial activation is regulated, in part by activation-induced cell death (AICD). Although many apoptotic aspects of the microglial AICD mechanism have been elucidated, little is known about the connection between the activation step and the death process. Using mouse primary microglial cultures, we show that the ectoenzyme CD38, via its calcium-mobilizing metabolite cyclic-ADP-ribose (cADPR), helps promote microglial activation and AICD induced by LPS plus IFNγ (LPS/IFNγ), suggesting that CD38 links the two processes. Accordingly, CD38 expression and activity, as well as intracellular calcium concentration ([Ca2+]i) in the primary microglia were increased by LPS/IFNγ treatment. Moreover, CD38 deficiency or treatment with cADPR antagonists conferred partial resistance to LPS/IFNγ-induced AICD and also reduced [Ca2+]i. Microglial activation, indicated by induced expression of nitric-oxide-synthase-2 mRNA and production of NO, secretion and mRNA expression of TNFα and IL-12 p40, and expression of IL-6 mRNA, was attenuated by CD38 deficiency or cADPR-antagonist treatment. The observed effects of CD38 on microglial activation is probably mediated via a cADPR-dependent increase in [Ca2+]i, and the effect on AICD by regulation of NO production. Our results thus suggest that CD38 significantly affects regulation of the amount and function of activated microglia, with important consequences for injury and repair processes in the brain.
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影响因子：
2.9
作者：
Dihné, M;Block, F;Töpper, R
通讯作者：
Töpper, R
影响因子：
15.9
作者：
Kreutzberg, GW
通讯作者：
Kreutzberg, GW
影响因子：
16
作者：
Hara, Y;Wakamori, M;Mori, Y
通讯作者：
Mori, Y
DOI：
10.1097/00005072-199509000-00010
发表时间：
1995-09-01
影响因子：
3.2
作者：
GEHRMANN, J;BANATI, RB
通讯作者：
BANATI, RB
影响因子：
3.9
作者：
Fliegert, R.;Gasser, A.;Guse, A. H.
通讯作者：
Guse, A. H.