Renal protection from ischemia mediated by A2A adenosine receptors on bone marrow-derived cells.
Renal protection from ischemia mediated by A2A adenosine receptors on bone marrow-derived cells.
复制标题
DOI：
10.1172/jci15483
复制
发表时间：
2003-09
期刊：
影响因子：
--
通讯作者：
Y. Day;Liping Huang;M. Mcduffie;D. Rosin;H. Ye;Jiang-fan Chen;M. Schwarzschild;J. Fink;J. Linden;M. Okusa
中科院分区：
文献类型：
--
作者：
Y. Day;Liping Huang;M. Mcduffie;D. Rosin;H. Ye;Jiang-fan Chen;M. Schwarzschild;J. Fink;J. Linden;M. Okusa
A2 A腺苷受体（A2 AR）的激活可保护肾脏免受缺血-再灌注损伤（IRI）。A2 AR在骨髓衍生（BM衍生）细胞和肾平滑肌、上皮和内皮细胞上表达。为了测量A2 AR对BM衍生细胞在抑制肾IRI中的贡献，我们检查了A2 AR的选择性激动剂ATL 146 e在嵌合小鼠中的作用，在嵌合小鼠中，BM通过致死性辐射消融，并用来自GFP、A2 AR-KO或WT小鼠的供体BM细胞重建，以产生GFP-->WT、A2 A-KO-->WT或WT-->WT小鼠嵌合体。我们发现，无论有无肾IRI，供体骨髓对肾血管内皮细胞的再增殖作用都很小或没有。ATL 146 e对A2 A-KO小鼠或A2 A-KO-->WT嵌合体中的IRI没有影响，但使IRI引起的血浆肌酐升高在WT小鼠中降低75%，在WT-->WT嵌合体中降低60%。ATL 146 e降低WT-->WT小鼠中IL-6、IL-1 β、IL-1 ra和TGF-α mRNA的诱导，但在A2 A-KO-->WT小鼠中不降低。IRI后，A2 A-KO小鼠的血浆肌酐显著高于WT小鼠，表明内源性腺苷具有一定的肾保护作用。我们的结论是，保护肾IRI的A2 AR激动剂或内源性腺苷需要激活受体表达的BM衍生细胞。
Activation of A2A adenosine receptors (A2ARs) protects kidneys from ischemia-reperfusion injury (IRI). A2ARs are expressed on bone marrow-derived (BM-derived) cells and renal smooth muscle, epithelial, and endothelial cells. To measure the contribution of A2ARs on BM-derived cells in suppressing renal IRI, we examined the effects of a selective agonist of A2ARs, ATL146e, in chimeric mice in which BM was ablated by lethal radiation and reconstituted with donor BM cells derived from GFP, A2AR-KO, or WT mice to produce GFP-->WT, A2A-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 A2A-KO mice or A2A-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-1beta, IL-1ra, and TGF-alpha mRNA in WT-->WT mice but not in A2A-KO-->WT mice. Plasma creatinine was significantly greater in A2A-KO than in WT mice after IRI, suggesting some renal protection by endogenous adenosine. We conclude that protection from renal IRI by A2AR agonists or endogenous adenosine requires activation of receptors expressed on BM-derived cells.