title: Macrophage A2A Adenosine Receptors Are Essential to Protect from Progressive Kidney Injury.
abstract: A2A adenosine receptors (A2ARs) are endogenous inhibitor of inflammation. Macrophages that are key effectors of kidney disease progression express A2ARs. We investigated the role of A2ARs in kidney inflammation in a macrophage-mediated anti-glomerular basement membrane reactive serum-induced immune nephritis in A2AR-deficient mice. Sub-threshold doses of glomerular basement membrane-reactive serum induced more severe and prolonged kidney damage with higher levels of proinflammatory cytokines and greater accumulation of inflammatory cells in A2AR(-/-) mice than wild-type (WT) mice. To investigate the role of macrophage A2AR in progressive kidney injury, glomerulonephritis was induced in CD11b-DTR transgenic mice. Macrophages were selectively depleted in the established phase of the disease and reconstituted with macrophages from WT or A2AR-deficient mice and then treated with an A2AR agonist. In mice receiving WT macrophages and treated with an A2AR agonist, the glomerular cellularity, crescent formation, sclerotic glomeruli, and tubulointerstitial injury were significantly reduced compared with the control group. In contrast, in mice reconstituted with A2AR-deficient macrophages and treated with an A2AR agonist, the kidney injury was more severe with increased deposition of collagen I, III, and IV. These findings suggest that disruption of the protective A2AR amplifies inflammation to accelerate glomerular damage and endogenous macrophage A2ARs are essential to protect from progressive kidney fibrosis.
authors: Department of Pathology, Baylor College of Medicine, Houston, Texas; Department of Pathology, Methodist Hospital, Houston, Texas.
authors: Luan D
authors: LD
authors: Truong
authors: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Denver, Aurora, Colorado.
authors: Jessica
authors: J
authors: Trostel
authors: Division of Gastroenterology, University of Colorado Denver, Aurora, Colorado.
authors: Rachel
authors: R
authors: McMahan
authors: Molecular Neuropharmacology Laboratory, Department of Neurology, Boston University School of Medicine, Boston, Massachusetts.
authors: Jiang-Fan
authors: JF
authors: Chen
authors: Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas. Electronic address: gabriela.garcia@ucdenver.edu.
authors: Gabriela E
authors: GE
authors: Garcia
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D050533:Glomerular Basement Membrane / Q000276:immunology / Q000473:pathology; D005921:Glomerulonephritis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000293:injuries / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism*
chemical_list: D058908:Adenosine A2 Receptor Agonists; D016207:Cytokines; D043705:Receptor, Adenosine A2A