CD95 (APO-1/Fas)-mediated apoptosis in colon epithelial cells: A possible role in ulcerative colitis

Background & Aims: Ligation of CD95 (APO-1/Fas) by antibody or CD95 ligand (CD95L) induces apoptosis and, in some cell lines, growth. Normal colonic epithelial cells constitutively express CD95. The function of CD95 on colonocytes is unknown. The aim of this study was to elucidate the role of epithelial CD95 in the normal colon and in ulcerative colitis. Methods: Intact colonic crypts were isolated, and the effects of CD95 ligation in vitro were studied. CD95L-expressing cells and apoptotic cells were detected in situ by RNA hybridization, immunohistochemistry, and DNA nick end labeling. Results: On CD95 ligation, isolated colonic crypt cells underwent apoptosis within 4 hours. No growth-promoting effect was observed. In normal colon, CD95L expression was restricted to few mononuclear cells randomly scattered within the lamina propria. Therefore, the CD95-CD95L system is very unlikely to operate in the regeneration of the colonic epithelium. However, in ulcerative colitis, the number of interstitial CD95L(+) cells and the frequency of apoptosis in both lamina propria and epithelium were increased considerably. Further, a focal association of subepithelial CD95L(+) mononuclear cells and epithelial apoptosis was observed. Conclusions: In ulcerative colitis, soluble CD95L-mediated epithelial apoptosis may lead to a breakdown of the epithelial barrier function facilitating the invasion of pathogenic microorganisms.