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H Ueyama
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 Background Keywords:
Fas ligand;
apoptosis;
ulcerative colitis;
reverse
transcription polymerase chain reaction;
T lymphocytes
The
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.
Aim
To analyse FasL
expression in affected colonic mucosa to ascertain Fas-FasL interaction
in ulcerative colitis.
Methods
FasL 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.
Results
FasL 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.
Conclusions
FasL 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)
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