Maintenance of the macromolecular barrier at cell extrusion sites in intestinal epithelium: Physiological rearrangement of tight junctions

Abstract

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 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-tracer show that the above described dynamic alterations in tight junctions at extrusion sites are generally sufficient to prevent transepithelial leaks of macromolecules.

Xylanase supplementation to a wheat-based diet alleviated the intestinal mucosal barrier impairment of broiler chickens challenged byClostridium perfringens

“…Apoptosis is a regulated process of cell death, and single epithelial cell apoptosis and extrusion without loss of barrier function are normal physiological events in the gastrointestinal tract (Madara, 1990;Abreu et al, 2000), but an increased epithelial apoptotic ratio might be another cause of relevant leaks in the epithelial barrier (Gitter et al, 2000). The present study demonstrated that epithelial apoptosis in all intestinal segments was considerably up-regulated in the challenged birds compared with the unchallenged birds, which suggested that C. perfringens challenge may disrupt epithelial barrier function by apoptosis-dependent mechanisms.…”

The Fate of Effete Epithelial Cells at the Villus Tips of the Human Small Intestine.

“…By freeze-fracture and light and electron microscopic studies, effete enterocytes at the villus tips of rat and hamster small intestine have been shown to extrude into the lumen, during which juctional complexes of extruding enterocytes with neighboring cells are maintained by proliferating juctional elements along the lateral margin of the cells (MADARA, 1990). As mentioned above, the apical cytoplasmic pieces at the villus tips of the guinea pig small intestine maintain junctional complexes with adjacent enterocytes, while the adjacent enterocytes form new junctional complexes beneath the exfoliating apical cytoplasmic pieces when they are exfoliated from the villus tips (IWANAGA et al, 1993).…”

“…The results indicate that macrophages in the lamina propria of the human small intestine do not participate in the exfoliating process of effete enterocytes. This notion is compatible with the present findings that the outward blebbing of effete enterocytes and apoptotic bodies were not detected at the villus tips, supporting the hypothesis that the shrinkage of effete enterocytes is mediated by inward blebbing, reflecting the presence of numerous clear vesicles in the cells.By freeze-fracture and light and electron microscopic studies, effete enterocytes at the villus tips of rat and hamster small intestine have been shown to extrude into the lumen, during which juctional complexes of extruding enterocytes with neighboring cells are maintained by proliferating juctional elements along the lateral margin of the cells (MADARA, 1990). As mentioned above, the apical cytoplasmic pieces at the villus tips of the guinea pig small intestine maintain junctional complexes with adjacent enterocytes, while the adjacent enterocytes form new junctional complexes beneath the exfoliating apical cytoplasmic pieces when they are exfoliated from the villus tips (IWANAGA et al, 1993).…”

Epithelial cell dynamics in rabbit cecum and proximal colon P1

“…A recently published study by Madara (1990) proposes that intestinal epithelial junctional complexes undergo dynamic changes when an exfoliating cell reaches the site of extrusion. Junctional complexes must be maintained to maintain the epithelial barrier, so complexes in adjacent migrating cells must also act in a similar dynamic fashion.…”