LOCALIZATION OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN ACUTE RENAL-ALLOGRAFT REJECTION IN THE RAT

There is increasing evidence for a role for nitric oxide (NO) in the a lloimmune response and induction of NO synthesis occurs during allogra ft rejection. The aim of this study was to investigate the source of N O synthesis in rejecting allografts. Localization of inducible nitric oxide synthase (iNOS) was studied by immunohistochemistry, in a rat mo del of acute renal allograft rejection, in unmodified Lewis recipients in which rejection is complete 7 days after transplantation of F-1 hy brid Lewis-Brown Norway kidneys. High levels of iNOS expression were f ound in infiltrating mononuclear cells in glomeruli and interstitium o f rejecting kidneys; there was no expression in parenchymal renal cell s, or in control isografts of either rat strain. Expression of iNOS in the cortex was present from 4 to 6 days posttransplantation, and had declined by the 7th day, where expression was principally in the medul la. The pattern of iNOS staining was similar to ED, staining, a marker for rat macrophages. These findings suggest that infiltrating macroph ages in the graft reaction are a prominent source of NO; this iNOS exp ression supports a role for NO in the modulation of local allogeneic r esponses, and possibly as a mediator of cytotoxic graft damage.