Analyses of the process to the chronic rejection after rat lung trasplantation.

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[Background and Purpose] Chronic rejection is the major cause of death intermediate- or long-term after lung transplantation. Its mechanism remains to be clearly demonstrated, but not a few data have shown that the frequency and severity of acute rejection are the risk factors for post-transplantation obstructive bronchitis considered as a manifestation of chronic rejection. Accordingly early detection and treatment of acute rejection is very important. After heart or pancreas transplantation, nitric oxide (NO) production have been reported to increase dramatically in accordance with acute rejection. We hypothesized that also after lung transplantation NO production would be a marker of acute rejection and investigated NO in exhaled air and NO production from bronchoalveolar cells after rat lung transplantation.[Material, Method and Results]Experiment 1(1995-1996) :In the 3 groups of orthotopic rat lung transplantation, allogenic (Brown-Norway to Lewis). +no treatment, allogenic+cyclos … More porin and isogenic (Lewis to Lewis), NO in exhaled air was determined on days 3, 5 after transplantation. NO in exhaled air were not different among the three groups on day 3, but on day 5 significantly (p<.Ol) high in the allogenic + no treatment group (63.9 * 39.2 ppb) compared with the allogenic+cyclosporin group (9.1 * 1.6) and isogenic group (6.9 * 0.5). Furthermore NO in exhaled air was significantly (p<.Ol) correlated with histological grading of acute rejection.Experiment 2(1996-1997) :In the 2 groups of orthotopic rat lung transplantation, allogenic (Brown-Norway to Lewis) + no treatment, isogenic (Lewis to Lewis), NO production from the cells collected by bronchoalveolar lavage and incubated for 3 hours was determined on days 3, 5 after transplantation, and also those cells were immunostained for iNOS.NO production was significantly (p<.Ol) high in the isogenic group (11.6 * 2.5 ppb) compared with the allogenic group (not detected) on day 3, and furthermore on day 5 (195.4 * 154.7 ppb). iNOS was stained on the recovered macrophages, lymphocytes and neutrophils.[Conclusion and Implication] NO in exhaled air would be a sensitive marker of acute rejection after lung transplantation, and furthermore NO production from the BAL cells would be also or more sensitive marker. Less