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CD45同工型RB作为对抗脂多糖诱导的小鼠小胶质细胞激活的分子靶点。

CD45 isoform RB as a molecular target to oppose lipopolysaccharide-induced microglial activation in mice.

作者信息

Townsend Kirk P, Vendrame Martina, Ehrhart Jared, Faza Brandon, Zeng Jin, Town Terrence, Tan Jun

机构信息

Neuroimmunology Laboratory, Institute for Psychiatry in Research, Department of Psychiatry and Behavioral Medicine, University of South Florida College of Medicine, 3515 East Fletcher Avenue, Tampa, FL 33613, USA.

出版信息

Neurosci Lett. 2004 May 13;362(1):26-30. doi: 10.1016/j.neulet.2004.01.082.

Abstract

CD45 is a membrane-bound protein tyrosine phosphatase expressed on all hemopoietic cells with multiple splice variants, including RA, RB, RC and RO. Our previous studies have shown that cross-linking of CD45 with an anti-CD45 antibody markedly inhibits LPS-induced microglia activation. In order to determine which of the CD45 isoforms may be responsible for these effects, we have investigated the expression of CD45 isoforms on cultured microglial cells using flow cytometric analysis. Data reveal that CD45RB is the predominant isoform expressed in murine primary cultured microglial cells. Furthermore, incubation of these cultured cells with anti-CD45RB antibody results in a reduction of microglial activation induced by LPS as evidenced by TNF-alpha production. As a validation of these findings in vivo, brain homogenates from anti-CD45RB antibody (MG23G2)-injected animals that had been treated with LPS demonstrate a significant decrease in TNF-alpha levels compared to control mice treated with LPS plus vehicle. Taken together, these findings suggest that therapeutic agents that specifically stimulate the microglial CD45RB signaling pathway may be effective in suppressing microglial activation associated with several neurodegenerative disorders.

摘要

CD45是一种膜结合蛋白酪氨酸磷酸酶,在所有造血细胞上表达,有多种剪接变体,包括RA、RB、RC和RO。我们之前的研究表明,用抗CD45抗体交联CD45可显著抑制脂多糖诱导的小胶质细胞活化。为了确定哪种CD45亚型可能介导这些效应,我们使用流式细胞术分析研究了培养的小胶质细胞上CD45亚型的表达。数据显示,CD45RB是在小鼠原代培养小胶质细胞中表达的主要亚型。此外,用抗CD45RB抗体孵育这些培养细胞会导致脂多糖诱导的小胶质细胞活化减少,这可通过肿瘤坏死因子-α的产生得到证明。作为这些体内研究结果的验证,与用脂多糖加赋形剂处理的对照小鼠相比,用脂多糖处理后注射抗CD45RB抗体(MG23G2)的动物的脑匀浆中肿瘤坏死因子-α水平显著降低。综上所述,这些发现表明,特异性刺激小胶质细胞CD45RB信号通路的治疗药物可能有效抑制与几种神经退行性疾病相关的小胶质细胞活化。

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