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[胞外嘌呤在导致脱髓鞘的炎症中的作用——治疗多发性硬化症的新方法]

[The role of ecto-purines in inflammation leading to demyelination - new means for therapies against multiple sclerosis].

作者信息

Cieślak Marek, Komoszyński Michał

机构信息

Wojewódzki Szpital Zespolony, Oddział Neurologiczny,Toruñ.

出版信息

Neurol Neurochir Pol. 2011 Sep-Oct;45(5):489-99. doi: 10.1016/s0028-3843(14)60318-2.

Abstract

Nucleotides released from activated and/or injured cells activate P2 receptors. Extracellular nucleotides serve as danger signals or damage-associated molecular patterns (DAMPs) that trigger various immune responses. Indeed, P2 receptors are highly expressed in the astrocytes, microglia and other immune cells such as T and B lymphocytes that migrate to the central nervous system. The activation of P2 receptors triggers the secretion of proinflammatory cytokines and chemokines as well as immune cell migration and proliferation that contribute to demyelination and axonal damage. The activation of P2 receptors is controlled by the ectonucleotidases which hydrolyze extracellular nucleotides. Ecto-NTPDases and ecto-5'-nucleotidase are expressed in the astrocytes, oligodendrocytes, microglia, endothelial cells and activated T cells. The hydrolysis of extracellular ATP and ADP by enzymes results in the generation of extracellular adenosine. This nucleoside interacts with P1 receptors and activates anti-inflammatory and immunosuppressive responses in the cells involved in MS.

摘要

从活化和/或受损细胞释放的核苷酸激活P2受体。细胞外核苷酸作为危险信号或损伤相关分子模式(DAMPs),触发各种免疫反应。事实上,P2受体在星形胶质细胞、小胶质细胞以及迁移到中枢神经系统的其他免疫细胞如T和B淋巴细胞中高度表达。P2受体的激活触发促炎细胞因子和趋化因子的分泌以及免疫细胞的迁移和增殖,这些都有助于脱髓鞘和轴突损伤。P2受体的激活由水解细胞外核苷酸的外核苷酸酶控制。外核苷酸三磷酸二磷酸酶和外5'-核苷酸酶在星形胶质细胞、少突胶质细胞、小胶质细胞、内皮细胞和活化的T细胞中表达。酶对细胞外ATP和ADP的水解导致细胞外腺苷的产生。这种核苷与P1受体相互作用,并在参与多发性硬化症的细胞中激活抗炎和免疫抑制反应。

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