CD95 (APO-1/Fas)-mediated apoptosis in colon epithelial cells: A possible role in ulcerative colitis
CD95 (APO-1/Fas)-mediated apoptosis in colon epithelial cells: A possible role in ulcerative colitis
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DOI：
10.1016/s0016-5085(97)70091-x
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发表时间：
1997-07-01
期刊：
影响因子：
29.4
通讯作者：
Moller, P
中科院分区：
文献类型：
--
作者：
Strater, J;Wellisch, I;Moller, P
背景与目的：CD 95（APO-1/Fas）与抗体或CD 95配体（CD 95 L）的连接可诱导细胞凋亡，并在某些细胞系中诱导生长。正常结肠上皮细胞组成型表达CD 95。CD 95在结肠细胞上的功能尚不清楚。本研究的目的是阐明上皮CD 95在正常结肠和溃疡性结肠炎中的作用。方法：分离完整的结肠隐窝，体外研究CD 95连接对结肠隐窝的影响。通过RNA杂交、免疫组织化学和DNA缺口末端标记法原位检测CD 95 L表达细胞和凋亡细胞。结果：CD 95连接后，分离的结肠隐窝细胞在4 h内发生凋亡。未观察到促生长作用。在正常结肠中，CD 95 L表达仅限于随机分散在固有层内的少数单核细胞。因此，CD 95-CD 95 L系统不太可能在结肠上皮的再生中起作用。而溃疡性结肠炎肠黏膜固有层和上皮细胞间质中CD 95 L（+）细胞的数量和凋亡率均显著增加。此外，观察到上皮下CD 95 L（+）单核细胞与上皮细胞凋亡的局灶性相关性。结论：在溃疡性结肠炎中，可溶性CD 95 L介导的上皮细胞凋亡可能导致上皮屏障功能的破坏，从而促进病原微生物的侵入。
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.