Epithelial integrity, cell death and cell loss in mammalian small intestine

In recent years, the different mechanisms of epithelial cell loss which occ ur in mammalian and avian small intestine have been re-investigated. Inform ation is now available for a variety of mammalian types and mechanisms can be divided into two major classes: [i] those preserving epithelial integrit y by maintaining intercellular tight junctions throughout early-to-late sta ges of cell extrusion; and [ii] those which compromise integrity by introdu cing breaches in epithelial continuity. Both classes are associated with th e activity and/or proximity of non-epithelial cells (mainly lymphocytes and mononuclear phagocytes) located in the epithelium or underlying lamina pro pria. Intraepithelial lymphocytes may be involved in enterocyte targetting and killing whilst lamina propria (LP) macrophages sequester cell debris. W here epithelial integrity is maintained, two types of loss can be identifie d. In the first (type 1), complete cells are extruded into the lumen. In th e second (type 2), only anucleate apical cell fragments pass into the lumen . There are two variants of type 2 loss distinguishable by the fate of the nucleated basal portions of cells. One variant (type 2a) creates large inte rcellular spaces extending from the preserved apical cap to the basal lamin a and containing enterocyte debris for phagocytosis. The second (type 2b) i nvolves the gradual shrinkage of individual cells (which become more electr on-dense) and in situ degeneration of their nucleated subapical portions in increasingly narrower intercellular spaces between adjacent healthy entero cytes. The mechanism of removal of these fragments is unclear but may be vi a macrophages or surrounding enterocytes. Apoptosis has been implicated in both type 1 and type 2 extrusion. In contrast, type 3 loss involves morphol ogical changes in enterocytes which are reminiscent of those seen in necros is and is accompanied by breaks in epithelial continuity following cell swe lling, a decrease in cell electron density and total or subtotal degradatio n of organelles and membranes. It ends in loss of either an abnormal cell a pex (with subsequent exposure of the degraded cell contents and their spill age into the lumen) or a complete cell remnant (extruded into the lumen bef ore total disintegration of plasma membranes).