title: Neutralization of the extracellular HMGB1 released by ischaemic damaged renal cells protects against renal ischaemia-reperfusion injury.
abstract: BACKGROUND
  Graft quality, comprised of ischaemia-reperfusion injury (IRI) and surgical manipulation, is one of the major factors influencing transplant rejection. High-mobility group box 1 (HMGB1), a known activator of innate immunity, has been associated with tissue-generated immunological 'danger' signals; however, its role in renal IRI is not clear.
  
  
  METHODS
  Renal IRI was induced by clamping the left renal pedicle for 60 min in uninephrectomized BALB/c mice. Rabbit anti-mouse HMGB1 antibody was given intraperitoneally 24 h and 30 min before renal ischaemia. Renal HMGB1 expression was assessed by immunohistochemistry and western blot. The therapeutic effect of HMGB1 neutralizing antibody on IRI was evaluated in terms of renal function, histological and immunopathologic examination and terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick end labelling assays.
  
  
  RESULTS
  Ischaemia alone was associated with release of HMGB1, which after reperfusion appeared to induce localization of HMGB1 to renal tubules, peritubular capillaries and glomeruli where the renal cells might be more susceptible to ischaemic insult. Administration of blocking antibody to HMGB1 was associated with reduction in tubular apoptosis and inflammation (TNF-α expression) in situ and in vivo with preservation of renal function.
  
  
  CONCLUSIONS
  These data suggest that released HMGB1 by ischaemic renal parenchyma cells may act as an essential early mediator in delayed inflammatory response during IRI, and targeting HMGB1 may represent a potential approach in the prevention of clinical IRI associated with kidney transplantation.
authors.affiliation: Institute of Organ Transplantation, Tongji Hospital, Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Li
authors.forename: Quan
authors.initials: Q
authors.lastname: Gong
authors.forename: Shan
authors.initials: S
authors.lastname: Zhong
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiang
authors.forename: Tomas E
authors.initials: TE
authors.lastname: Ichim
authors.forename: Cong-Yi
authors.initials: CY
authors.lastname: Wang
authors.forename: Shi
authors.initials: S
authors.lastname: Chen
authors.forename: Feili
authors.initials: F
authors.lastname: Gong
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000276:immunology*; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015427:Reperfusion Injury / Q000276:immunology / Q000503:physiopathology*
chemical_list: D024243:HMGB1 Protein