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-NG-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.
Garside
P
P
Department of Immunology, University of Glasgow, Western Infirmary, Scotland.
Hutton
A K
AK
Severn
A
A
Liew
F Y
FY
Mowat
A M
AM
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002455:Cell Division; D005260:Female; D006086:Graft vs Host Disease / Q000473:pathology*; D007422:Intestines / Q000473:pathology*; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D009569:Nitric Oxide / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019323:omega-N-Methylarginine
D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine