GUT 1998;43:48-55 ( July )

High Fas ligand expression on lymphocytes in lesions of ulcerative colitis

H Ueyama,^a T Kiyohara,^a N Sawada,^a K Isozaki,^a S Kitamura,^a S Kondo,^a J Miyagawa,^a S Kanayama,^a Y Shinomura,^a H Ishikawa,^b T Ohtani,^b R Nezu,^c S Nagata,^d Y Matsuzawa^a

^a Second Department of Internal Medicine, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan, ^b Department of Cancer Epidemiology, Research Institute, Osaka Medical Center for Cancer and Cardiovascular Diseases, 3-3 Nakamichi 1-chome Higashinari-ku, Osaka 537, Japan, ^c First Department of Surgery, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan, ^d Department of Genetics, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan

Correspondence to: Dr H Ueyama.

Accepted for publication 4 February 1998

BackgroundThe pathogenesis of ulcerative colitis is unclear, but cytotoxic T lymphocytes infiltrating the mucosa have been implicated in mucosal damage. The Fas ligand (FasL), expressed on cytotoxic T lymphocytes, induces apoptosis in cells expressing Fas.
AimTo analyse FasL expression in affected colonic mucosa to ascertain Fas-FasL interaction in ulcerative colitis.
MethodsFasL mRNA was quantified in colonic mucosal specimens from healthy subjects and patients with ulcerative colitis or Crohn's disease, using the competitive reverse transcription polymerase chain reaction. FasL mRNA localisation was determined by in situ hybridisation. Expression of Fas in colonic mucosa was analysed immunohistochemically. Phenotypes of lamina propria lymphocytes that expressed FasL were analysed by flow cytometry.
ResultsFasL mRNA was strongly expressed in active ulcerative colitis lesions, but not in those associated with active Crohn's disease or active proctitis-type ulcerative colitis. In situ hybridisation showed that FasL mRNA expression occurred in mononuclear cells infiltrating lesions. Fas was expressed in epithelial cells in ulcerative colitis and Crohn's disease, and in normal subjects. Cytometry showed that FasL was expressed in CD3 lymphocytes infiltrating the lamina propria in active lesions.
ConclusionsFasL is expressed in CD3 lymphocytes infiltrating into ulcerative colitis but not Crohn's disease lesions, suggesting that Fas-FasL induced apoptosis participates in the mucosal damage of ulcerative colitis.
(GUT 1998;43:48-55)

Keywords: Fas ligand;  apoptosis;  ulcerative colitis;  reverse transcription polymerase chain reaction;  T lymphocytes

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© 1998 by Gut
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