title: Ischemia-reperfusion injury in renal transplantation is independent of the immunologic background.
abstract: BACKGROUND
  Adhesion molecule expression is important to early transplant failure. However, whether or not adhesion molecule-facilitated inflammation is antigen-dependent is unknown. We tested this hypothesis.
  
  
  METHODS
  Rat renal grafts were four-hours cold-preserved in University of Wisconsin (UW) solution, transplanted to syngeneic or allogeneic recipients, and harvested after 2, 6, 12, 24, and 48 hours and after 1 week. The first allogeneic group receive no immunosuppression; two additional groups received either low (1.5 mg/kg) or standard (5 mg/kg) cyclosporine A (CsA). Renal function and morphology were determined; frozen sections were immunostained for P-selectin, L-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1), leukocyte function associated molecule-1 (LFA-1), very late antigen-4 (VLA-4), as well as for neutrophils and monocytes.
  
  
  RESULTS
  Selectins increased rapidly at 2 hours and quickly decreased by 12 hours. While P-selectin was expressed on vasculature, L-selectin was found on inflammatory cells. Neutrophil influx and that of LFA-1-positive cells occurred early, peaked between 12 and 24 hours, and paralleled the maximal impairment in renal function. ICAM-1 and PECAM-1 showed similar kinetics and a diffuse distribution. VCAM-1 increased more slowly after 12 hours, peaked at 24 hours, and was localized predominantly on the endothelium of elastic vessels. Between 24 hours and 1 week, all grafts progressively developed dense VLA-4-positive monocytic infiltrates adjacent to vessels expressing VCAM-1. Functional, morphological, and immunohistochemical parameters did not differ between isografts and allografts at one week. However, by day 10, allografts showed severe vascular and cellular rejection, while injury in isografts resolved. Immunosuppression with CsA did not reverse the inflammation induced by ischemia-reperfusion injury.
  
  
  CONCLUSIONS
  The early inflammation after ischemia-reperfusion injury is largely independent of the immunologic background. We suggest that initial injury prevention should receive the highest priority.
authors.affiliation: Franz Volhard Clinic at the Max Delbrück Center for Molecular Medicine, Medical Faculty of the Charité, Humboldt University of Berlin, Berlin, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Dragun
authors.forename: U
authors.initials: U
authors.lastname: Hoff
authors.forename: J K
authors.initials: JK
authors.lastname: Park
authors.forename: Y
authors.initials: Y
authors.lastname: Qun
authors.forename: W
authors.initials: W
authors.lastname: Schneider
authors.forename: F C
authors.initials: FC
authors.lastname: Luft
authors.forename: H
authors.initials: H
authors.lastname: Haller
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D006084:Graft Rejection / Q000473:pathology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008297:Male; D009336:Necrosis; D009393:Nephritis / Q000209:etiology; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D019087:Selectins / Q000378:metabolism; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
chemical_list: D015815:Cell Adhesion Molecules; D007166:Immunosuppressive Agents; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D019087:Selectins; D016572:Cyclosporine