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 C Racusen, Abdel R 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

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Fas Ligand Protein
Reperfusion Injury
Leukocytes
Kidney
Acute Kidney Injury
T-Lymphocytes
Mutation
T-Lymphocyte Subsets
Creatinine
Lymph Nodes
Bone Marrow
Inflammation

ASJC Scopus subject areas

  • Nephrology

Cite this

Blocking fas ligand on leukocytes attenuates kidney ischemia-reperfusion injury. / Ko, Gang Jee; Jang, Hye Ryoun; Huang, Yanfei; Womer, Karl L.; Liu, Manchang; Higbee, Elizabeth; Xiao, Zuoxiang; Yagita, Hideo; Racusen, Lorraine C; Hamad, Abdel R; Rabb, Hamid.

In: Journal of the American Society of Nephrology, Vol. 22, No. 4, 04.2011, p. 732-742.

Research output: Contribution to journalArticle

Ko, GJ, Jang, HR, Huang, Y, Womer, KL, Liu, M, Higbee, E, Xiao, Z, Yagita, H, Racusen, LC, Hamad, AR & Rabb, H 2011, 'Blocking fas ligand on leukocytes attenuates kidney ischemia-reperfusion injury', Journal of the American Society of Nephrology, vol. 22, no. 4, pp. 732-742. https://doi.org/10.1681/ASN.2010010121
Ko, Gang Jee ; Jang, Hye Ryoun ; Huang, Yanfei ; Womer, Karl L. ; Liu, Manchang ; Higbee, Elizabeth ; Xiao, Zuoxiang ; Yagita, Hideo ; Racusen, Lorraine C ; Hamad, Abdel R ; Rabb, Hamid. / Blocking fas ligand on leukocytes attenuates kidney ischemia-reperfusion injury. In: Journal of the American Society of Nephrology. 2011 ; Vol. 22, No. 4. pp. 732-742.
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