MAINTENANCE OF THE MACROMOLECULAR BARRIER AT CELL EXTRUSION SITES IN INTESTINAL EPITHELIUM - PHYSIOLOGICAL REARRANGEMENT OF TIGHT JUNCTIONS
MAINTENANCE OF THE MACROMOLECULAR BARRIER AT CELL EXTRUSION SITES IN INTESTINAL EPITHELIUM - PHYSIOLOGICAL REARRANGEMENT OF TIGHT JUNCTIONS
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DOI：
10.1007/bf01868675
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发表时间：
1990-06-01
影响因子：
2.4
通讯作者：
MADARA, JL
中科院分区：
文献类型：
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作者：
MADARA, JL
所有的上皮斯劳垂死的细胞，但这一生理过程的后果上皮屏障功能是未知的。在哺乳动物小肠中，吸收细胞从绒毛基部迁移到绒毛顶端，并从绒毛顶端脱落斯劳。这些绒毛尖端挤出区通常被设想为大分子可以穿过上皮渗漏的部位。然而，即使根据已知的上皮更新率，挤出事件每天发生数百万次，也只有痕量的大分子穿过该上皮。在这里，我们研究的特点，上皮屏障大分子渗透在绒毛尖端挤出区大鼠和仓鼠。冷冻断裂，光镜和电镜研究表明，挤压细胞不会留下短暂的孔，因为他们从上皮提升。相反，当细胞挤出时，相邻细胞的突起在它们下面延伸。此外，紧密连接元件增殖之间的挤压细胞和它们的邻居，并出现向下移动的横向边缘的挤压细胞，因为它延伸到管腔。这些观察结果表明，新形成的连接元件“拉链”的上皮关闭挤压进行，从而防止上皮不连续发生。使用辣根过氧化物酶作为大分子示踪剂的相关体内灌注实验表明，上述挤压部位紧密连接的动态变化通常足以防止大分子的跨上皮渗漏。
All epithelia slough dying cells but the consequences of this physiological process to epithelial barrier function is unknown. In mammalian small intestine absorptive cells are known to migrate from the villus base to the villus tip from which they slough. These villus tip extrusion zones are often envisioned as sites at which macromolecules could leak across the epithelium. However, only trace amounts of macromolecules across this epithelium even though, based on known epithelial turnover rates, extrusion events occur millions of times daily. Here, we examine the characteristics of the epithelial barrier to macromolecular permeation at villus tip extrusion zones in rats and hamsters. Freeze-fracture, light and electron microscope studies reveal that extruding cells do not leave transient holes behind as they lift from the epithelium. Rather, as cells extrude, processes of adjacent cells extend under them. Moreover, tight junction elements proliferate between extruding cells and their neighbours and appear to move down the laeral margin of the extruding cell as it extends into the lumen. These observations suggest that newly formed junctional elements "zipper" the epithelium closed as extrusion proceeds thus preventing epithelial discontinuities from occurring. Correlative in vivo perfusion experiemnts using horseradish peroxidase as a macromolecular-tracer show that the above described dynamic alterations in tight junctions at extrusion sites are generally sufficient to prevent transepithelial leaks of macromolecules.