NITRIC-OXIDE MEDIATES INTESTINAL PATHOLOGY IN GRAFT-VS-HOST DISEASE

We have investigated the involvement of nitric oxide (NO) in intestinal graft-vs. -host reaction (GvHR) in mice. Treatment of mice with L-N(G)-monomethyl arginine (L-NMMA), a specific inhibitor of NO synthesis, abolished the mucosal pathology of intestinal GvHR and reduced the associated lymphocytic infiltration of the epitheliUM. L-NMMA had no effect on splenomegaly in GvHR, nor did it interfere with the growth of an undifferentiated crypt stem cell line, or the production of tumor necrosis factor-alpha by activated macrophages in vitro. In contrast, L-NMMA inhibited the enhanced activity of natural killer (NK) cells which occurs in GvHR. We conclude that a NO-dependent mechanism is essential for intestinal immunopathology in GvHR and that this may reflect a role for NO in NK cell function.