Nitric oxide mediates intestinal pathology in graft-vs.-host disease

Eur J Immunol. 1992 Aug;22(8):2141-5. doi: 10.1002/eji.1830220827.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Cell Division
  • Female
  • Graft vs Host Disease / pathology*
  • Intestines / pathology*
  • Killer Cells, Natural / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred CBA
  • Nitric Oxide / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism
  • omega-N-Methylarginine

Substances

  • Tumor Necrosis Factor-alpha
  • omega-N-Methylarginine
  • Nitric Oxide
  • Arginine