Blocking Fas Ligand on Leukocytes Attenuates Kidney Ischemia-Reperfusion Injury
- 1 April 2011
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American Society of Nephrology
- Vol. 22 (4), 732-742
- https://doi.org/10.1681/asn.2010010121
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.Keywords
This publication has 41 references indexed in Scilit:
- Fas-Mediated Apoptosis Regulates the Composition of Peripheral αβ T Cell Repertoire by Constitutively Purging Out Double Negative T CellsPLOS ONE, 2008
- Normal mouse kidneys contain activated and CD3+CD4−CD8− double-negative T lymphocytes with a distinct TCR repertoireJournal of Leukocyte Biology, 2008
- Blockade of the Fas/Fas ligand interaction suppresses hepatocyte apoptosis in ischemia-reperfusion rat liverApoptosis, 2008
- Protection from Autoimmune Diabetes and T-Cell Lymphoproliferation Induced by FasL Mutation Are Differentially Regulated and Can Be Uncoupled PharmacologicallyThe American Journal of Pathology, 2007
- Fas ligand exerts its pro‐inflammatory effects via neutrophil recruitment but not activationImmunology, 2007
- A Novel Treatment for Ocular Tumors Using Membrane FasL Vesicles to Activate Innate Immunity and Terminate Immune PrivilegeInvestigative Ophthalmology & Visual Science, 2005
- Endothelial Cell Overexpression of Fas Ligand Attenuates Ischemia-Reperfusion Injury in the HeartPublished by Elsevier BV ,2003
- Treatment of acute renal failureKidney International, 1998
- Agonistic anti-Fas antibodies induce glomerular cell apoptosis in mice in vivoKidney International, 1997
- Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomasNature, 1995