Chemokine receptor 5 blockade modulates macrophage trafficking in renal ischaemic-reperfusion injury
- Yoo, Kyung Don; Cha, Ran-hui; Lee, Sunhwa; Kim, Ji Eun; Kim, Kyu Hong; Lee, Jong Soo; Kim, Dong Ki; Kim, Yon Su; Yang, Seung Hee
- Issue Date
- acute kidney injury; bilateral ischaemia-reperfusion injury; CC chemokine receptor 5; chemokine; macrophage
- Journal of Cellular and Molecular Medicine, v.24, no.10, pp.5515 - 5527
- Journal Title
- Journal of Cellular and Molecular Medicine
- Start Page
- End Page
- 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.
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- 2. Clinical Science > Department of Nephrology and Hypertension > 1. Journal Articles
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