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Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: role of macrophages.
- Source :
-
American Journal of Physiology: Renal Physiology . Apr2005, Vol. 288, pF722-F731. 10p. 2 Diagrams, 2 Charts, 6 Graphs. - Publication Year :
- 2005
-
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 (A2A) receptors (A2ARs) 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 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 A2ARs. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1931857X
- Volume :
- 288
- Database :
- Academic Search Index
- Journal :
- American Journal of Physiology: Renal Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 16571273
- Full Text :
- https://doi.org/10.1152/ajprenal.00378.2004