Free radical-mediated tissue injury in acute lung allograft rejection and the effect of superoxide dismutase

BACKGROUND: The role of monocytes and neutrophils is crucial during acute allograft rejection. They have the capacity to generate toxic reactive oxygen intermediates in response to specific agonists that may act as tissue destructive molecules. We examined the possibility of reactive intermediate-mediated tissue injury in acute lung allograft rejection, as well as the effect of superoxide dismutase. METHODS: Allogenic (Brown Norway to F344) or syngenic (F344 to F344) rat left-lung transplantation was performed. Generation of reactive oxygen intermediates in peripheral blood was evaluated by the method of luminol-dependent chemiluminescence. Cell membrane phospholipid peroxidation in the graft was measured as malondialdehyde concentration. The third group of animals having allografts received bovine erythrocyte superoxide dismutase (5,000 U/kg intravenously every 12 hours after transplantation). RESULTS: Relative chemiluminescence response in the allograft recipient to normal F344 was elevated on postoperative day 1 (257%), then decreased slightly on day 3 (156%) and was elevated again on day 7 (560%) as the process of rejection progressed. Allograft tissue malondialdehyde levels (248.37 +/- 112.35 nM/whole lung, n = 6; p < 0.05 by Student's t test) were higher than isograft levels (139.29 +/- 35.93 nM/whole lung, n = 6) on day 7. Superoxide dismutase treatment significantly ameliorated the histologic degree of rejection on day 7. CONCLUSIONS: These results demonstrate the tissue destructive activity of reactive oxygen intermediates during lung allograft rejection. To scavenge free radicals may be a useful therapeutic modality in the management of acute lung allograft rejection.