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 li gand (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 elucidat e tile role of epithelial CD95 in the normal colon and in ulcerative c olitis. Methods: Intact colonic crypts were isolated, and the effects of CD95 ligation in vitro were studied. CD95L-expressing cells and apo ptotic cells were detected in situ by RNA hybridization, immunohistoch emistry, and DNA nick end labeling. Results: On CD95 ligation, isolate d colonic crypt cells underwent apoptosis within 4 hours. No growth-pr omoting effect was observed. In normal colon, CD95L expression was res tricted 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 o f apoptosis in both lamina propria and epithelium were increased consi derably. Further, a focal association of subepithelial CD95L(+) mononu clear cells and epithelial apoptosis was observed. Conclusions: In ulc erative colitis, soluble CD95L-mediated epithelial apoptosis may lead to a breakdown of the epithelial barrier function facilitating the inv asion of pathogenic microorganisms.