Structural changes in the plasma membrane accompanying differentiation of epithelial cells in human and monkey small intestine

Abstract

The activity of most enzymes associated with microvillus membranes increases as immature small intestinal epithelial cells differentiate and migrate from crypt to villus. Also, it has been suggested that crypt epithelium may be more permeable to small molecules than villus epithelium. We used freeze-fracture techniques to determine whether the number of microvillus intramembrane particles (IMPs) (which are thought to represent integral membrane proteins), or the dimensions and organization of tight junctions (which may relate to epithelial permeability) change during maturation of human jejunal and monkey jejunal and ileal epithelium. Intramembrane particles were systematically counted on microvilli from the lower crypt to the upper villus. Tight-junction depth, strand number, and organization were also assessed. As crypt cells mature and migrate onto the villus, the average density of microvillus protoplasmic face intramembrane particles more than doubles in human jejunum, in monkey jejunum, and in monkey ileum. Goblet cell and caveolated cell microvilli were relatively particle poor. Depth of tight junctions from crypt to villus surface increased in human and monkey jejunum and in monkey ileum. Likewise, the number of strands was greater in villus than in crypt tight junctions for all three tissues studied. Tight junctions became more organized on the villus, losing the aberrant strands found in the crypt. Monkey ileal tight junctions were deeper and had more strands than monkey jejunal tight junctions. Goblet cell tight junctions varied greatly in structure from cell to cell. In the crypts, rounded, presumably mitotic cells displayed extensive loose strands that resembled tight junction elements, but were scattered over the entire basolateral membrane. In conclusion, (a) the reported increase in specific activity of microvillus membrane enzymes as absorptive cells migrate from crypt to villus is accompanied by an increase in IMPs; (b) tight junctions between crypt cells are less deep and less organized than those between villus cells, suggesting that the crypt epithelium may be more permeable than that of the villus; (c) the depth and strand numbers of villus tight junctions are greater in the ileum than in the jejunum, paralleling known regional permeability differences; and (d) because the population of tight junctions within the intestinal epithelium is heterogeneous, the permeability of the epithelium as a whole may reflect this heterogeneity, rather than being solely dependent on the tight-junction structure of the villus absorptive cells.