Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, College of Preventive Medicine, Third Military Medical University, Chongqing, China.
Lab Invest. 2011 Mar;91(3):462-71. doi: 10.1038/labinvest.2010.182. Epub 2010 Nov 1.
Dying epithelial cells are thought to be squeezed out of the epithelium by the contraction of an actomyosin ring formed in live neighboring cells, which simultaneously closes any potential gap, thereby maintaining the integrity of the epithelial layer. The shrinkage and contraction of apoptotic cells contribute little to the extrusion process. In contrast, the clearance of dying intestinal columnar epithelial cells in vivo usually leaves a transient gap via an unknown mechanism. By using freshly isolated small intestinal villus units with or without basal lamina, we found that the nucleus of apoptotic enterocytes moved apically until they budded off, leaving the cytoplasmic residue in the transient gap. Apical polarity of nucleus movement was restricted unless the basal lamina was artificially removed. F-actin mainly accumulated in apoptotic cells rather than neighboring live cells, even after the addition of resistance force against extrusion. The actin accumulation in apoptotic cells does not depend on the living state of neighboring cells. Apoptotic cells can complete the shedding process when neighboring a goblet cell, as the majority of space is occupied by mucin granules and the cytoplasm consists of intermediate filaments and microtubules, but lacks F-actin. We found that the elongation and deformation of apoptotic cells depend on the stretching force generated inside the cell, rather than the force generated by neighboring cells extending. Our findings clearly demonstrate that intestinal epithelial shedding does not depend on the formation and contraction of an actomyosin ring in live neighboring cells. Apoptotic epithelial cells may undergo an active process of cell deformation with adhesion-restricted polarity, which may contribute to maintaining barrier function during a high rate of cellular turnover.
人们认为，濒死的上皮细胞是被活的邻近细胞中形成的肌动球蛋白环的收缩挤出上皮的，同时封闭任何潜在的间隙，从而维持上皮层的完整性。凋亡细胞的收缩和收缩对挤出过程贡献很小。相比之下，体内死亡的肠柱状上皮细胞的清除通常通过未知机制留下一个短暂的间隙。通过使用带有或不带有基底膜的新鲜分离的小肠绒毛单位，我们发现凋亡肠上皮细胞的核向上移动，直到它们萌芽，留下细胞质残留在短暂的间隙中。核运动的顶端极性受到限制，除非基底膜被人为去除。F-肌动蛋白主要在凋亡细胞中积累，而不是在邻近的活细胞中，即使在施加抵抗挤出的阻力后也是如此。凋亡细胞中的肌动蛋白积累不依赖于邻近细胞的存活状态。当邻近杯状细胞时，凋亡细胞可以完成脱落过程，因为大部分空间被粘蛋白颗粒占据，细胞质由中间丝和微管组成，但缺乏 F-肌动蛋白。我们发现凋亡细胞的伸长和变形取决于细胞内产生的拉伸力，而不是由伸展的邻近细胞产生的力。我们的发现清楚地表明，肠上皮细胞的脱落不依赖于活邻近细胞中肌动球蛋白环的形成和收缩。凋亡上皮细胞可能经历一个具有黏附受限极性的主动细胞变形过程，这可能有助于在高细胞周转率期间维持屏障功能。
