Leaks in the epithelial barrier caused by spontaneous and TNF-alpha-induced single-cell apoptosis

Current opinion assumes epithelial integrity during spontaneous apoptotic c ell death. We measured, for the first time, the local conductances associat ed with apoptoses and show leaks of up to 280 nS (mean 48 +/- 19 nS) in hum an intestinal epithelium, The results disprove the dogma that isolated cell apoptosis occurs without affecting the epithelial cell permeability barrie r, After induction by tumor necrosis factor alpha (TNF-alpha) the apoptotic leaks were dramatically enhanced: not only was the frequency increased by threefold, but the mean conductance also increased by 12-fold (597+/-98 nS) , Thus, apoptosis accounted for about half (56%) of the TNF-alpha-induced p ermeability increase whereas the other half was caused by degradation of ti ght junctions in nonapoptotic areas. Hence, spontaneous and induced apoptos is hollow out the intestinal barrier and may facilitate loss of solutes and uptake of noxious agents.