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

Abstract

Summary. Until recently, little has been known about the morphological features of dying enterocytes at the villus tips of the human small intestine. The present study aimed to show the exfoliating processes of effete enterocytes at the villus tips. Cellular elements of the duodenal lumen and jejunal tissue in humans were fixed and processed for DNA nick end labeling (TUNEL), and transmission and scanning electron microscopy (TEM and SEM). Most cellular elements in the duodenal lumen were enterocytes having TUNEL-positive nuclei. By SEM, protruding enterocytes were discerned at the villus tips. Using the SEM samples embedded in epoxy resin, protruding enterocytes were observed at the villus tips by TEM; they were shrunk by forming numerous clear and autophagic vacuoles, took dome-like profiles, and possessed nuclei with chromatin condensation. The intercellular spaces beneath these protruding or effete enterocytes were often occupied by large lymphocytes. By TUNEL reaction, positive stainings appeared in the epithelium not only at the tip of the villi but also around the site. The results suggest that effete enterocytes at the villus tips of human small intertine are first shrunk by forming clear and autophagic vacuoles, and showed that their nuclei exhibit chromatin condensation immediately before being exfoliated into the lumen.It is generally believed that enterocytes (columnar epithelial cells) of mammalian guts are generated in crypts and move towards the villus tips, where they die by apoptosis, being exfoliated into the lumen (LEBLOND and MESSIER, 1958; MACDONALD et al., 1964; CHENG and LEBLOND, 1974; EASTWOOD, 1977; LEBLOND, 1981;WRIGHT and ALISON, 1984). According to the morphological criteria of apoptosis, dying cells show chromatin condensation and cell shrinkage, followed by heterophagocytosis (WYLLIE et al., 1980(WYLLIE et al., , 1984 KERR et al., 1987; CLARKE, 1990). Recently, GAVRIELI et al. (1992) have used in situ nick end labeling of dUTP mediated by terminal deoxytransferase (TUNEL reaction) to show that DNA fragmentation appears in epithelial cells of the rat and mouse small intestine and human large intestine at the villus tips. However, dying enterocytes with morphological features of apoptosis are hardly seen at the villus tips (KERB et al., 1987).In the small intestine of guinea pigs, IWANAGA et al. (1993) have shown that intraepithelial lymphocytes and subepithelial macrophages are involved in removing effete enterocytes at the tips of villi. They demonstrated that the body of the effete enterocytes was removed by those cells, whereas their thin superficial layer was retained to be later exfoliated without destroying the barrier; these cell fragments could be recognized in the fluid collected from the ileal lumen. Until recently, however, there have been neither morphological nor biochemical reports on the fate of effete enterocytes in the human small intestine at the tip of villi. To investigate this problem, the present study examined the dying processes of effete enterocytes ...

Apoptosis: The History and Trends of Its Studies.

“…Apoptosis 1. Where and when apoptosis occurs Apoptosis generally occurs for the maintenance of correct cell numbers in various tissues (KERB and SEARLE, 1973;WYLLIE et al, 1973a, b;HUN et al, 1993;IWANAGA et al, 1993;NAKAMURA et al, 1995;SHIBAHARA et al, 1995), in embryogenesis (SAUNDERS, 1966;SAUNDERS and FALLON, 1966;O'CONNOR and WYTTENBACH, 1974;TANIGUCHI et al, 1995;TAKASHITA et al, 1995), in metamorphosis (LOCKSHIN and ZEKERI, 1991), and in various sorts of tissue disorders including tumor regression (COPE and WILLIE, 1991), ischemia (KERR, 1965(KERR, , 1971NITATORI et al, 1995;IKEDA et al, 1995), nervous diseases (CLARKE, 1991 ;Lo et al, 1995), exposure to toxins (O'SHEA et al, 1978;SUZUKI et al, 1995), and tissue atrophy (KERB and SEAPLE, 1973;ABE and WATANABE, 1995).…”

“…Cytotoxic T lymphocytes usually kill virally infected cells, tumor cells and allogeneic cells (DUKE, 1991). Even for the physiological maintenance of correct cell numbers have they been suggested to participate in the regulation of cell death in the guinea pig small intestinal epithelium (HAN et al, 1993;IWANAGA et al, 1993;IWANAGA, 1995).…”

“…Using the method of in situ nick end labeling of biotinylated dUTP mediated by terminal deoxynucleotidyl transferase, TUNEL, which can detect the 3'-OH end of DNA double strands breaking, epithelial cell death at the villus tip of the human small intestine has been examined; TUNEL-positive enterocytes are easily found around the villus tip, whereas effete enterocytes with marginally chromatin-condensed nuclei are hardly seen there (SHIBAHARA et al, 1995). Moreover, NITATORI et al (1995) have shown that although the CAl pyramidal cells of the gerbil hippocampus are positively stained by TUNEL reaction 3 days after brief ischemia, no chromatin condensation in the cells is detected at this stage by electron microscopy.…”

“…3, 5, 6). In the villus tip of the human small intestine, effete enterocytes reduce basal parts of the cytoplasm by forming clear vesicles; they also contain numerous large autophagolysosomes (SHIBAHARA et al, 1995) (Figs. 3, 5).…”

“…Apoptosis in epithelial cells due to detachment from the extracellular matrix As stated above, effete enterocytes reduce basal parts of the cytoplasm at the villus tip of the human small intestine by forming clear vesicles due to the inward blebbing of the cell membrane before they undergo apoptosis (SHIBAHARA et al, 1995). Integrins are known to be primarily responsible for the adhesion of cells to extracellular matrices (ECM).…”