Summary
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.
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References
Atisook, K., Carlson, S., Madara, J.L. 1990. Effects of phlorizin and sodium on glucose-elicited alterations of cell junctions in intestinal epithelia.Am. J. Physiol. 258:C77-C85
Cooper, M., Teichberg, S., Lifshitz, F. 1978. Alterations in rat jejunal permeability to a macromolecular tracer during a hypersomatic load.Lab. Invest. 38:447–452
Hudspeth, A.J. 1975. Establishment of tight junctions between epithelial cells.Proc. Natl. Acad. Sci. USA 72:2711–2713
Kachar, B., Pinto da Silva, P. 1981. Rapid massive assembly of tight junction strands.Science 213:541–543
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 York
Madara, J.L. 1989. Loosening tight junctions: Lessons from the intestine.J. Clin. Invest. 83:1089–1094
Madara, J.L., Moore, R., Carlson, S. 1987. Alteration of intestinal tight junction structure and permeability by cytoskeletal contraction.Am. J. Physiol. 253:C854-C861
Madara, J.L., Pappenheimer, J.R. 1987. Structural basis for physiological regulation of paracellular pathways in intestinal epithelia.J. Membrane Biol. 100:149–164
Madara, J.L., Trier, J.S. 1980. Structural abnormalities of jejunal epithelial cell membranes in celiac sprue.Lab. Invest. 43:254–261
Madara, J.L., Trier, J.S. 1982. Structure and permeability of goblet cell tight junctions in rat small intestine.J. Membrane Biol. 66:145–157
Madara, J.L., Trier, J.S., Neutra, M.R. 1980. Structural changes in the plasma membrane accompanying differentiation of epithelial cells in human and monkey small intestine.Gastroenterology 78:963–975
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. 56:424–434
Powell, D. 1981. Barrier function of epithelia.Am. J. Physiol. 241:6275–6288
Rhodes, R.S., Karnovsky, M.J. 1971. Loss of macromolecular barrier function associated with surgical trauma to the intestine.Lab. Invest. 25:220–228
Walker, W.A. 1981. Intestinal transport of macromolecules.In: Physiology of the Gastrointestinal Tract L.R. Johnson. editor. pp. 1271–1286. Raven, New York
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Madara, J.L. Maintenance of the macromolecular barrier at cell extrusion sites in intestinal epithelium: Physiological rearrangement of tight junctions. J. Membrain Biol. 116, 177–184 (1990). https://doi.org/10.1007/BF01868675
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DOI: https://doi.org/10.1007/BF01868675