Maintenance of the macromolecular barrier at cell extrusion sites in intestinal epithelium: Physiological rearrangement of tight junctions
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All epithelia slough dying cells but the consequences of this physiological process to epithelial barrier functions 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 cross 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 neighbors and appear to move down the lateral 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 experiments using horseradish peroxidase as a macromolecular-tracershow that the above described dynamic alterations in tight junctions at extrusion sites are generally sufficient to prevent transepithelial leaks of macromolecules.
Key Wordstight junction tight junction regulation
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- 5.Lipkin, M. 1987. Proliferation and differentiation of normal and diseased gastrointestinal cells.In: Physiology of the Gastrointestinal Tract. L.R. Johnson, editor. pp. 255–284. Raven, New YorkGoogle Scholar
- 8.Madara, J.L., Pappenheimer, J.R. 1987. Structural basis for physiological regulation of paracellular pathways in intestinal epithelia.J. Membrane Biol. 100:149–164Google Scholar
- 10.Madara, J.L., Trier, J.S. 1982. Structure and permeability of goblet cell tight junctions in rat small intestine.J. Membrane Biol. 66:145–157Google Scholar
- 12.Marcial, M.A., Madara, J.L. 1981. Analysis of absorptive cell occluding junction structure-function relationships in a state of enhanced junctional permeability.Lab. Invest. 56:424–434Google Scholar
- 13.Powell, D. 1981. Barrier function of epithelia.Am. J. Physiol. 241:6275–6288Google Scholar
- 15.Walker, W.A. 1981. Intestinal transport of macromolecules.In: Physiology of the Gastrointestinal Tract L.R. Johnson. editor. pp. 1271–1286. Raven, New YorkGoogle Scholar