Ischemia-reperfusion injury in renal transplantation is independent of theimmunologic background

Background. Adhesion molecule expression is important to early transplant f ailure. 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 W isconsin (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 recei ved either low (1.5 mg/kg) or standard (5 mg/kg) cyclosporine A (CsA). Rena l function and morphology were determined; frozen sections were immunostain ed for P-selectin, L-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), platelet endothelial cell adhes ion 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-l-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 an d a diffuse distribution. VCAM-1 increased more slowly after 12 hours, peak ed at 24 hours, and was localized predominantly on the endothelium of elast ic vessels. Between 24 hours and 1 week, all grafts progressively developed dense VLA-Il-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 inflamm ation induced by ischemia-reperfusion injury. Conclusions. The early inflammation after ischemia-reperfusion injury is la rgely independent of the immunologic back-ground. We suggest that initial i njury prevention should receive the highest priority.