title: Enhancing complement control on endothelial barrier reduces renal post-ischemia dysfunction.
abstract: BACKGROUND
  Excessive complement activation is an integral part of ischemia and reperfusion (IR) injury (IRI) of organs. In kidney transplantation, the pathologic consequence of IRI and complement activation can lead to delayed graft function, which in turn is associated with acute rejection. Previous strategies to reduce complement-induced IRI required systemic administration of agents, which can lead to increased susceptibility to infections/immune diseases. The objective of this study was to determine whether an increase in complement control defenses of rat kidney endothelium reduces IRI. We hypothesized that increased complement control on the endothelial barrier reduces IR-mediated complement activation and reduces kidney dysfunction.
  
  
  METHODS
  Fischer 344 rats underwent left kidney ischemia for 45 min and treatment with a novel fusogenic lipid vesicle (FLVs) delivery system to decorate endothelial cells with vaccinia virus complement control protein (VCP), followed by reperfusion for 24 h. Assessment included renal function by serum creatinine and urea, myeloperoxidase assay for neutrophil infiltration, histopathology, and quantification of C3 production in kidneys.
  
  
  RESULTS
  Animals in which the kidney endothelium was bolstered by FLVs+VCP treatment had better renal function with a significant reduction in serum creatinine compared with vehicle controls (P < 0.05). Also, C3 production was significantly reduced (P < 0.05) in treated animals compared with vehicle controls.
  
  
  CONCLUSIONS
  Increasing complement control at the endothelial barrier with FLVs+VCP modulates complement activation/production during the first 24 h, reducing renal dysfunction following IRI.
authors.affiliation: Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Sathnur B
authors.initials: SB
authors.lastname: Pushpakumar
authors.forename: Gustavo
authors.initials: G
authors.lastname: Perez-Abadia
authors.forename: Chirag
authors.initials: C
authors.lastname: Soni
authors.forename: Rong
authors.initials: R
authors.lastname: Wan
authors.forename: Nathan
authors.initials: N
authors.lastname: Todnem
authors.forename: Phani K
authors.initials: PK
authors.lastname: Patibandla
authors.forename: Tathyana
authors.initials: T
authors.lastname: Fensterer
authors.forename: Qunwei
authors.initials: Q
authors.lastname: Zhang
authors.forename: John H
authors.initials: JH
authors.lastname: Barker
authors.forename: Claudio
authors.initials: C
authors.lastname: Maldonado
mesh_terms: D000818:Animals; D003167:Complement Activation / Q000187:drug effects / Q000502:physiology*; D003176:Complement C3 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007674:Kidney Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D007677:Kidney Function Tests; D008081:Liposomes / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D014508:Urea / Q000097:blood; D014764:Viral Proteins / Q000494:pharmacology*
chemical_list: D003176:Complement C3; D008081:Liposomes; D014764:Viral Proteins; C066459:complement-control protein, Vaccinia virus; D014508:Urea; D003404:Creatinine; D009195:Peroxidase