Macrophage A2A Adenosine Receptors Are Essential to Protect from Progressive Kidney Injury

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 2016 Aug 14

PMID 27520357

Citations 13

Authors

Luan D Truong

Jessica Trostel

Rachel McMahan

Jiang-Fan Chen

Gabriela E Garcia

Affiliations

Soon will be listed here.

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.

Citing Articles

Adenosine A2A Receptor Activation Alleviated Disease of Mice with Systemic Infection by Regulating Macrophage Function.

Wu X, Dong K, Liu Y, Yang L, Zhang J, Yang M J Inflamm Res. 2025; 18:3283-3294.

PMID: 40065909 PMC: 11892491. DOI: 10.2147/JIR.S501546.

Production of Acetylcholine by Podocytes and its Protection from Kidney Injury in GN.

Truong L, Trostel J, Roncal C, Cara-Fuentes G, Miyazaki M, Miyazaki-Anzai S J Am Soc Nephrol. 2024; 36(2):205-218.

PMID: 39302734 PMC: 11801748. DOI: 10.1681/ASN.0000000000000492.

Monocytes and Macrophages in Kidney Disease and Homeostasis.

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CD73-generated extracellular adenosine promotes resolution of neutrophil-mediated tissue injury and restrains metaplasia in pancreatitis.

OBrien B, Faraoni E, Strickland L, Ma Z, Mota V, Mota S FASEB J. 2022; 37(1):e22684.

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Cathepsin D interacts with adenosine A receptors in mouse macrophages to modulate cell surface localization and inflammatory signaling.

Skopal A, Keki T, Toth P, Csoka B, Koscso B, Nemeth Z J Biol Chem. 2022; 298(5):101888.

PMID: 35367412 PMC: 9065627. DOI: 10.1016/j.jbc.2022.101888.

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