Alterations in mRNA for inducible and endothelial nitric oxide synthase and plasma nitric oxide with rejection and/or infection of allotransplanted lungs

Abstract

Background. Experiments were designed to determine expression of type II (iNOS) and type III (ecNOS) nitric oxide synthase in lung parenchyma and systemic endothelial cells with rejection and/or infection of single lung allografts. Methods. After single lung allotransplantation, dogs were maintained on standard triple immunosuppressive therapy for 5 days and then placed into one of three groups. Group I (n=4) was maintained on immunosuppressants, group II (n=7) immunosuppression was withdrawn to allow acute rejection of the allograft, and group III (n=6) infection was induced by bronchoscopic inoculation of Escherichia coli. Results. At postoperative days 7-9, no histological evidence of rejection or infection was observed in transplanted lungs of group I. In lungs of group II, rejection ranged from mild to severe; in lungs of group III, infection was severe. Some animals had both rejection and infection (n=8) and were studied separately. Plasma levels of nitric oxide increased comparably with rejection and/or infection compared to preoperative values. Expression of mRNA for ecNOS decreased significantly in lung parenchyma but not in aortic endothelial cells from dogs of groups II and III. However, expression of mRNA for iNOS increased with both rejection and/or infection in both lung parenchyma and aortic endothelial cells. Conclusions. iNOS is induced locally within the graft and systemically in aortic endothelial cells with rejection and/or infection of lung allografts. Plasma levels of nitric oxide are elevated with both rejection and infection and may not be useful in the differential diagnosis of these processes after lung transplantation.