1. Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: role of macrophages.
- Author
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Yuan-Ji Day, Liping Huang, Hong Ye, Linden, Joel, and Okusa, Mark D.
- Subjects
REPERFUSION injury ,ISCHEMIA ,BLOOD circulation disorders ,KIDNEY injuries ,MACROPHAGES ,PHAGOCYTES ,ACUTE kidney failure ,SMALL interfering RNA - Abstract
The role of monocytes/macrophages in the pathogenesis of ischemia-reperfusion injury ORB is unknown. We sought to determine whether activation of macrophage adenosine 2A (A
2A ) receptors (A2A Rs) mediates tissue protection We subjected C57B1/6 mice infused with clodronate [dichloromethylene bisphosphonate (Cl2 MBP)] 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 Cl2 MBP (26% of control). Adoptive transfer of murine RAW 264.7 cells reconstituted injury, an effect blocked significantly by A2A agonists (27% of plasma creatinine from mice reconstituted with macrophages). Macrophages subjected to A2A 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 A2A agonists (20% of vehicle treatment). Finally, the A2A agonist effect on IRI was blocked in macrophage-depleted A2A -knockout mice reconstituted with wild-type RAW 264.7 cells. RNase protection assays 24 h after IRI demonstrated that macrophages are required for IL-6 and TGF-β mRNA induction. However, A2A agonist-mediated tissue protection is independent of IL-6 and TGF-β mRNA. We conclude that the full extent of IRI requires macrophages and that A2A agonist-mediated tissue protection is independent of activation of macrophage A2A Rs. [ABSTRACT FROM AUTHOR]- Published
- 2005
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