Role of CXC chemokine receptor 3 pathway in renal ischemic injury
Role of CXC chemokine receptor 3 pathway in renal ischemic injury
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DOI：
10.1681/asn.2005090954
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发表时间：
2006-03-01
影响因子：
13.6
通讯作者：
Abdi, Reza
中科院分区：
文献类型：
--
作者：
Fiorina, Paolo;Ansari, Mohammed Javeed;Abdi, Reza
趋化因子在炎症中募集白细胞和调节辅助性T细胞1(Th1)/Th2免疫反应中发挥重要作用。这些机制在肾缺血再灌注(I/R)损伤的发病机制中起重要作用。CXC趋化因子受体3(CXCR3)受体与其配体的相互作用是促进炎症和增强Th1免疫应答的关键致病途径。在诱导小鼠肾缺血模型后，观察到肾内CXCR3及其配体的表达增加。与野生型(WT)小鼠相比，CXCR3缺陷小鼠(CXCR3(-/-))的血清肌酐水平显著降低，存活率显著提高，急性肾小管坏死和细胞浸润显著减少。在肾脏中，从肾脏中恢复的浸润性细胞的细胞内染色显示，与WT小鼠相比，CXCR3(-/-)小鼠的CD4(+)干扰素-伽马(+)细胞的百分比较低。此外，在诱导I/R损伤前将WT CD3(+)细胞过继转移到CXCR3(-/-)小鼠体内，取消了CXCR3(-/-)小鼠对I/R损伤的保护作用。结论：CXCR3在Th1细胞向缺血肾脏的募集和介导I/R损伤中起重要作用，可能成为治疗I/R损伤的新靶点。
Chemokines play a major role in the recruitment of leukocytes in inflammation and in the regulation of T helper 1 (Th1)/Th2 immune responses. These mechanisms have been recognized to be important in the pathogenesis of renal ischemia-reperfusion (I/R) injury. The interaction of the CXC chemokine receptor 3 (CXCR3) receptor with its ligands is a key pathogenic pathway in promoting inflammation and in enhancing Th1 immune responses. After the induction of ischemia in the mouse model of renal ischemia, an increase in intrarenal expression of CXCR3 and its ligands was observed. Compared with the wild-type (WT) mice, CXCR3-deficient mice (CXCR3(-/-)) had significantly lower serum creatinine levels, better survival rate, and significantly less acute tubular necrosis and cellular infiltrates. In the kidney, intracellular staining of infiltrating cells that were recovered from kidneys revealed a lower percentage of CD4(+)IFN-gamma(+) cells in the CXCR3(-/-) mice compared with the WT mice. Furthermore, adoptive transfer of WT CD3(+) cells into CXCR3(-/-) mice before induction of I/R injury abrogated the protection of CXCR3(-/-) mice from I/R injury. It is concluded that CXCR3 plays an important role in orchestrating the recruitment of Thl cells to the ischemic kidney and in mediating I/R injury and therefore may serve as a novel target for the therapy of I/R injury.