Chemokine receptor 5 blockade modulates macrophage trafficking in renal ischaemic‐reperfusion injury
Open Access
- 30 March 2020
- journal article
- research article
- Published by Wiley in Journal of Cellular and Molecular Medicine
- Vol. 24 (10), 5515-5527
- https://doi.org/10.1111/jcmm.15207
Abstract
Chemokine receptor 5 (CCR5) is a pivotal regulator of macrophage trafficking in the kidneys in response to an inflammatory cascade. We investigated the role of CCR5 in experimental ischaemic‐reperfusion injury (IRI) pathogenesis. To establish IRI, we clamped the bilateral renal artery pedicle for 30 min and then reperfused the kidney. We performed adoptive transfer of lipopolysaccharide (LPS)‐treated RAW 264.7 macrophages following macrophage depletion in mice. B6.CCR5−/− mice showed less severe IRI based on tubular epithelial cell apoptosis than did wild‐type mice. CXCR3 expression in CD11b+ cells and inducible nitric oxide synthase levels were more attenuated in B6.CCR5−/− mice. B6.CCR5−/− mice showed increased arginase‐1 and CD206 expression. Macrophage‐depleted wild‐type mice showed more injury than B6.CCR5−/− mice after M1 macrophage transfer. Adoptive transfer of LPS‐treated RAW 264.7 macrophages reversed the protection against IRI in wild‐type, but not B6.CCR5−/− mice. Upon knocking out CCR5 in macrophages, migration of bone marrow‐derived macrophages from wild‐type mice towards primary tubular epithelial cells with recombinant CCR5 increased. Phospho‐CCR5 expression in renal tissues of patients with acute tubular necrosis was increased, showing a positive correlation with tubular inflammation. In conclusion, CCR5 deficiency favours M2 macrophage activation, and blocking CCR5 might aid in treating acute kidney injury.Keywords
Funding Information
- Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea Grant (HI11C0631)
- Young Investigator Research Grant from the Korean Society of Nephrology (KSN 2017)
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