Renal protection from ischemia mediated by A2A adenosine receptors on bone marrow–derived cells

Activation of A 2A adenosine receptors (A 2A Rs) protects kidneys from ischemia-reperfusion injury (IRI).A 2A Rs are expressed on bone marrow-derived (BM-derived) cells and renal smooth muscle, epithelial, and endothelial cells.To measure the contribution of A 2A Rs on BM-derived cells in suppressing renal IRI, we examined the effects of a selective agonist of A 2A Rs, ATL146e, in chimeric mice in which BM was ablated by lethal radiation and reconstituted with donor BM cells derived from GFP, A 2A R-KO, or WT mice to produce GFP→WT, A 2A -KO→WT, or WT→WT mouse chimera.We found little or no repopulation of renal vascular endothelial cells by donor BM with or without renal IRI.ATL146e had no effect on IRI in A 2A -KO mice or A 2A -KO→WT chimera, but reduced the rise in plasma creatinine from IRI by 75% in WT mice and by 60% in WT→WT chimera.ATL146e reduced the induction of IL-6, IL-1β, IL-1ra, and TGF-α mRNA in WT→WT mice but not in A 2A -KO→WT mice.Plasma creatinine was significantly greater in A 2A -KO than in WT mice after IRI, suggesting some renal protection by endogenous adenosine.We conclude that protection from renal IRI by A 2A R agonists or endogenous adenosine requires activation of receptors expressed on BM-derived cells.