Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: role of macrophages
Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: role of macrophages
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DOI：
10.1152/ajprenal.00378.2004
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发表时间：
2005-04-01
影响因子：
4.2
通讯作者：
Okusa, MD
中科院分区：
文献类型：
--
作者：
Day, YJ;Huang, L;Okusa, MD
肾缺血再灌注损伤和腺苷2a受体介导的组织保护：巨噬细胞的作用。 Am J Physiol Renal Physiol 288：F722-F731，2005。首次发表于 2004 年 11 月 23 日；doi:10.1152/ajprenal。 00378.2004.-单核细胞/巨噬细胞在缺血再灌注损伤（IRI）发病机制中的作用尚不清楚。我们试图确定巨噬细胞腺苷 2A (A(2A)) 受体 (A(2A)Rs) 的激活是否介导组织保护。我们对注射了氯膦酸盐 [二氯亚甲基二膦酸盐 (Cl2MBP)] 的 C57B1/6 小鼠进行 IRI（缺血 32 分钟，然后再灌注 24 小时）以消耗其巨噬细胞。 IRI 引起血浆肌酐升高，而 Cl2MBP 则降低了血浆肌酐升高（对照的 26%）。小鼠 RAW 264.7 细胞的过继转移可重建损伤，A(2A) 激动剂（巨噬细胞重建小鼠血浆肌酐的 27%）可显着阻断这种效应。通过小干扰RNA进行A(2A)敲除的巨噬细胞被过继转移到巨噬细胞耗尽的小鼠中并重建损伤（对照小鼠的110%）；然而，血浆肌酐的增加被 A(2A) 激动剂阻断（媒介物治疗的 20%）。最后，在用野生型 RAW 264.7 细胞重建的巨噬细胞耗尽的 A2A 敲除小鼠中，A(2A) 激动剂对 IRI 的作用被阻断。 IRI 后 24 小时进行的 RNase 保护测定表明，巨噬细胞是 IL-6 和 TGF-β mRNA 诱导所必需的。然而，A(2A) 激动剂介导的组织保护独立于 IL-6 和 TGF-β mRNA。我们得出结论，IRI 的全部范围需要巨噬细胞，并且 A(2A) 激动剂介导的组织保护独立于巨噬细胞 A(2A)R 的激活。
Renal ischemia-reperfusion injury and adenosine 2a receptor-mediated tissue protection: role of macrophages. Am J Physiol Renal Physiol 288: F722-F731, 2005. First published November 23, 2004;doi:10.1152/ajprenal. 00378.2004.-The role of monocytes/ macrophages in the pathogenesis of ischemia-reperfusion injury ( IRI) is unknown. We sought to determine whether activation of macrophage adenosine 2A (A(2A)) receptors (A(2A)Rs) mediates tissue protection. We subjected C57B1/6 mice infused with clodronate [dichloromethylene bisphosphonate (Cl2MBP)] to IRI (32 min of ischemia followed by 24 h of reperfusion) to deplete them of macrophages. IRI induced an elevation of plasma creatinine that was reduced with Cl2MBP (26% of control). Adoptive transfer of murine RAW 264.7 cells reconstituted injury, an effect blocked significantly by A(2A) agonists (27% of plasma creatinine from mice reconstituted with macrophages). Macrophages subjected to A(2A) knockout by small interfering RNA were adoptively transferred to macrophage-depleted mice and reconstituted injury (110% of control mice); however, the increase in plasma creatinine was blocked by A(2A) agonists (20% of vehicle treatment). Finally, the A(2A) agonist effect on IRI was blocked in macrophage-depleted A2A-knockout mice reconstituted with wildtype RAW 264.7 cells. RNase protection assays 24 h after IRI demonstrated that macrophages are required for IL-6 and TGF-beta mRNA induction. However, A(2A) agonist-mediated tissue protection is independent of IL-6 and TGF-beta mRNA. We conclude that the full extent of IRI requires macrophages and that A(2A) agonist-mediated tissue protection is independent of activation of macrophage A(2A)Rs.