title: Blocking Fas ligand on leukocytes attenuates kidney ischemia-reperfusion injury.
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.
authors: Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Gang Jee
authors: GJ
authors: Ko
authors: Hye Ryoun
authors: HR
authors: Jang
authors: Yanfei
authors: Y
authors: Huang
authors: Karl L
authors: KL
authors: Womer
authors: Manchang
authors: M
authors: Liu
authors: Elizabeth
authors: E
authors: Higbee
authors: Zuoxiang
authors: Z
authors: Xiao
authors: Hideo
authors: H
authors: Yagita
authors: Lorraine
authors: L
authors: Racusen
authors: Abdel Rahim A
authors: AR
authors: Hamad
authors: Hamid
authors: H
authors: Rabb
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D053222:Fas Ligand Protein / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D053148:Caspase 3