TNF-alpha-mediated expression of the receptor for anaphylatoxin C5a on neurons in experimental Listeria meningoencephalitis.
TNF-alpha-mediated expression of the receptor for anaphylatoxin C5a on neurons in experimental Listeria meningoencephalitis.
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DOI：
10.4049/jimmunol.159.2.861
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发表时间：
1997-07
影响因子：
4.4
通讯作者：
P. Stahel;Karl Frei;H. Eugster;Adriano Fontana;Klaus M. Hummel;Rick A. Wetsel;Robert S. Ames;S. Barnum
中科院分区：
文献类型：
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作者：
P. Stahel;Karl Frei;H. Eugster;Adriano Fontana;Klaus M. Hummel;Rick A. Wetsel;Robert S. Ames;S. Barnum
过敏毒素 C5a 作为蛛网膜下腔炎症的有效介质，与细菌性脑膜炎的发病机制有关。我们研究了患有实验性单核细胞增生李斯特菌 (LM) 脑膜脑炎的小鼠大脑中 C5a 受体 (C5aR) 的表达。在疾病过程中，发现脑膜和脑室的浸润细胞表达C5aR mRNA和蛋白质。在脑实质中，锥体神经元和浦肯野细胞上观察到非常低的组成型 C5aR 表达。然而，在感染 LM 的小鼠中，感染后 6 小时开始，神经元上的 C5aR 表达急剧增加，并在 24 至 36 小时之间达到最大。 TNF-α 被确定为神经元 C5aR 表达的重要介质，因为缺乏 TNF 和淋巴毒素-α 基因的小鼠（TNF/淋巴毒素-α -/- 小鼠）在 LM 感染后表现出 C5aR 表达显着减弱。此外，ip。即使在没有细菌感染的情况下，注射重组 TNF-α 也能诱导 TNF/淋巴毒素-α -/- 小鼠和正常动物大脑中 C5aR 表达增强。我们还评估了传染性脑膜炎患者脑脊液中过敏毒素 C5a 的水平。在所有细菌性脑膜炎患者 (n = 9)、18 名无菌性脑膜炎患者中的 6 名以及 66 名对照患者中的 1 名中检测到 C5a。实验性李斯特菌脑膜炎神经元上 TNF-α 介导的 C5aR 表达的发现以及感染性脑膜炎人类患者脑脊液中配体 C5a 的检测，为研究导致继发性脑损伤的病理生理学后遗症提供了新的方向。
The anaphylatoxin C5a has been implicated in the pathogenesis of bacterial meningitis as a potent mediator of inflammation in the subarachnoid space. We investigated the expression of the receptor for C5a (C5aR) in brains of mice with experimental Listeria monocytogenes (LM) meningoencephalitis. In the course of the disease, infiltrating cells in the meninges and the ventricles were found to express C5aR mRNA and protein. In the brain parenchyma, very low constitutive C5aR expression was seen on pyramidal neurons and Purkinje cells. However, in LM-infected mice, a dramatic increase in C5aR expression occurred on neurons starting 6 h after infection and was maximal between 24 and 36 h. TNF-alpha was identified as an essential mediator of neuronal C5aR expression, since mice lacking the genes for TNF and lymphotoxin-alpha (TNF/lymphotoxin-alpha -/- mice) showed significantly attenuated C5aR expression after LM infection. Furthermore, i.p. injection of recombinant TNF-alpha induced enhanced C5aR expression in the brains of TNF/lymphotoxin-alpha -/- mice and in normal animals even in the absence of a bacterial infection. We also assessed the levels of anaphylatoxin C5a in the cerebrospinal fluid of patients with infectious meningitis. C5a was detected in all patients with bacterial meningitis (n = 9), in 6 of 18 patients with aseptic meningitis, and in 1 of 66 control patients. The finding of TNF-alpha-mediated C5aR expression on neurons in experimental Listeria meningitis and the detection of the ligand, C5a, in the cerebrospinal fluid of human patients with infectious meningitis present new directions in the investigation of the pathophysiologic sequelae leading to secondary brain damage.