Blocking fas ligand on leukocytes attenuates kidney ischemia-reperfusion injury

Gang Jee Ko, Hye Ryoun Jang, Yanfei Huang, Karl L. Womer, Manchang Liu, Elizabeth Higbee, Zuoxiang Xiao, Hideo Yagita, Lorraine Racusen, Abdel Rahim A. Hamad, Hamid Rabb

Research output: Contribution to journalArticle

Abstract

Inflammation contributes to the pathogenesis of ischemic acute kidney injury (AKI), and T cells mediate the early phase of ischemia-reperfusion injury (IRI). The Fas/Fas ligand (FasL) pathway modulates the balance of T cell subsets in the peripheral circulation as well as multiple inflammatory responses, suggesting that FasL may mediate ischemic AKI. Here, we induced bilateral renal IRI in mice bearing a loss-of-function mutation of FasL (the gld mutation) and in wild-type mice. Compared with wild-type mice, serum creatinine was lower in gld mice (1.4 ± 0.9 mg/dl versus 2.6 ± 0.4) at 24 hours after IRI (P < 0.05). In addition, gld mice had fewer TNF-α-producing T lymphocytes in the kidneys and renal lymph nodes. Furthermore, pharmacologic blockade of FasL protected the kidneys of wild-type mice from IRI. Analysis of bone marrow chimeric mice suggested that the pathogenic effect of FasL involves leukocytes; reconstitution of wild-type mice with gld splenocytes attenuated IRI. In contrast, reconstitution of gld mice with wild-type splenocytes enhanced IRI. These data demonstrate that FasL, particularly on leukocytes, mediates ischemic AKI.

Original languageEnglish (US)
Pages (from-to)732-742
Number of pages11
JournalJournal of the American Society of Nephrology
Volume22
Issue number4
DOIs
StatePublished - Apr 2011

ASJC Scopus subject areas

  • Nephrology

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    Ko, G. J., Jang, H. R., Huang, Y., Womer, K. L., Liu, M., Higbee, E., Xiao, Z., Yagita, H., Racusen, L., Hamad, A. R. A., & Rabb, H. (2011). Blocking fas ligand on leukocytes attenuates kidney ischemia-reperfusion injury. Journal of the American Society of Nephrology, 22(4), 732-742. https://doi.org/10.1681/ASN.2010010121