The blocking of CXCR3 and CCR5 suppresses the infiltration of T lymphocytes in rat renal ischemia reperfusion.
The blocking of CXCR3 and CCR5 suppresses the infiltration of T lymphocytes in rat renal ischemia reperfusion.
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DOI：
10.1093/ndt/gfs360
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发表时间：
2012-10
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影响因子：
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通讯作者：
K. Tsutahara;M. Okumi;Y. Kakuta;T. Abe;K. Yazawa;S. Miyagawa;K. Matsunami;H. Otsuka;J. Kaimori;S. Takahara;N. Nonomura
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作者：
K. Tsutahara;M. Okumi;Y. Kakuta;T. Abe;K. Yazawa;S. Miyagawa;K. Matsunami;H. Otsuka;J. Kaimori;S. Takahara;N. Nonomura
背景最近的研究已确定 T 细胞和自然杀伤 T (NKT) 细胞是肾缺血再灌注 (I/R) 损伤的重要介质。这些细胞的募集是由趋化因子诱导的。我们使用大鼠肾缺血再灌注损伤模型研究了拮抗剂 (TAK) 阻断 CXCR3 和 CCR5 的效果。方法对Sprague-Dawley大鼠进行假手术或左肾闭塞45 min后进行再灌注和对侧肾切除。对照组或TAK组分别在钳夹前30分钟注射磷酸盐缓冲盐水或TAK。评估血清肌酐、肾小管损伤、趋化因子表达和浸润细胞。结果 与对照组相比，TAK 治疗显着抑制了血清肌酐的升高（假手术 0.40 ± 0.05 mg/dL，对照组 2.86 ± 0.67 mg/dL，TAK 1.60 ± 0.73 mg/dL），并导致肾小管损伤评分较低（假手术 0，对照组 4.8 ± 0.3，TAK 3.3 ± 1）。各组缺血后肾脏中与CXCR3和CCR5结合的趋化因子的mRNA表达在再灌注1小时后升高。此外，与假手术组相比，对照组CD4+ T细胞和CD8+ NKT细胞的浸润增加，并且TAK注射显着抑制了CD4+ T细胞的数量（假手术13.5±3.5×10(4)细胞，对照28.9±15.4×10(4)细胞，TAK 11.8±3.5×10(4)细胞）和CD8+的数量。 NKT 细胞（假手术 11.7 ± 5.4 × 10(4) 细胞，对照 30.1 ± 8.6 × 10(4) 细胞，TAK 11.8 ± 2.9 × 10(4) 细胞）。结论 这些研究结果表明，阻断 CXCR3 和 CCR5 可抑制 T 细胞和 NKT 细胞的浸润，并对 I/R 损伤的肾脏具有保护作用。
BACKGROUND Recent studies have identified T cells and natural killer T (NKT) cells as important mediators in renal ischemia-reperfusion (I/R) injury. The recruitment of these cells is induced by chemotaxis factors. We investigated the effects of blocking CXCR3 and CCR5 by an antagonist (TAK) using a rat renal I/R injury model. METHODS The Sprague-Dawley rats were either subjected to sham operation or left renal occlusion for 45 min followed by reperfusion and contralateral nephrectomy. The control or TAK groups were, respectively, injected phosphate-buffered saline or TAK at 30 min prior to clamp. Serum creatinine, tubular injury, chemokines expression and infiltrating cells were assessed. RESULTS TAK treatment significantly suppressed the elevation in serum creatinine (sham 0.40 ± 0.05 mg/dL, control 2.86 ± 0.67 mg/dL, TAK 1.60 ± 0.73 mg/dL) and resulted in a lower tubular injury score compared with the control group (sham 0, control 4.8 ± 0.3, TAK 3.3 ± 1). The mRNA expression of chemokines that bind to CXCR3 and CCR5 in the post-ischemic kidneys was elevated at 1 h after reperfusion in each group. Moreover, the infiltration of CD4+ T cells and CD8+ NKT cells in the control group increased compared with the sham group and TAK injection significantly suppressed the number of CD4+ T cells (sham 13.5 ± 3.5 × 10(4) cells, control 28.9 ± 15.4 × 10(4) cells, TAK 11.8 ± 3.5 × 10(4) cells) and the number of CD8+ NKT cells (sham 11.7 ± 5.4 × 10(4) cells, control 30.1 ± 8.6 × 10(4) cells, TAK 11.8 ± 2.9 × 10(4) cells). CONCLUSIONS These findings suggest that the blocking of CXCR3 and CCR5 suppress the infiltration of T cells and NKT cells and have a protective effect on kidneys that are injured by I/R.