Secretagogue response of goblet cells and columnar cells in human colonic crypts

Abstract

Crypts of Lieberkühn were isolated from human colon, and differential interference contrast microscopy distinguished goblet and columnar cells. Activation with carbachol (CCh, 100 μM) or histamine (10 μM) released contents from goblet granules. Stimulation with prostaglandin E2(PGE2, 5 μM) or adenosine (10 μM) did not release goblet granules but caused the apical margin of columnar cells to recede. Goblet volume was lost during stimulation with CCh or histamine (∼160 fl/cell), but not with PGE2 or adenosine. Three-quarters of goblet cells were responsive to CCh but released only 30% of goblet volume. Half-time for goblet volume release was 3.7 min. PGE2 stimulated a prolonged fluid secretion that attained a rate of ∼350 pl/min. Columnar cells lost ∼50% of apical volume during maximal PGE2 stimulation, with a half-time of 3.3 min. In crypts from individuals with ulcerative colitis, goblet cells were hypersensitive to CCh for release of goblet volume. These results support separate regulation for mucus secretions from goblet cells and from columnar cells, with control mechanisms restricting total release of mucus stores.

Defective goblet cell exocytosis contributes to murine cystic fibrosis–associated intestinal disease

“…The paucity of the WT exocytotic events and extended recording times confounded a direct measurement of WT exocytotic rate, but the rate of change in granule area after switching to 115 mM HCO 3 -KBR was -5.6 ± 1.9 μm 2 /min (P < 0.05 vs. 0; n = 6-7). Although the change in granule area as a measure of exocytosis may be affected by unappreciated changes in granule or cell hydration, the longitudinal axis of the granule cluster in WT goblet cells decreased, whereas the transverse axis did not change (Δlong axis = -2.3 ± 0.4 μm, P < 0.05; Δtranverse axis = -0.5 ± 0.3 μm, NS), which is consistent with changes in granule cluster morphology in human colonic goblet cells undergoing stimulated exocytosis as compared with nonresponding goblet cells (47 Figure 5D, the switch to isethionate KBR did not affect the granule area of either WT or Cftr-KO goblet cells. The effects of high luminal HCO 3 -concentrations on goblet cell function may have physiological relevance.…”

“…For WT goblet cells, 115 mM HCO 3 -luminal superfusion induced a moderate rate of exocytosis. Although observation of spontaneous exocytosis was rare, parameters consistently indicating WT goblet cell exocytosis were decreased granular area and morphological changes in the granule cluster indicative of exocytosis (47). Further, 115 mM luminal HCO 3 -greatly increased granule area in the Cftr-KO goblet cell, which was reminiscent of the early stages of CCH stimulation.…”

Intrarectal Dehydroleucodine Suppresses Trinitrobenzene Sulfonic Acid–Induced Colitis in Rats, A Model for Inflammatory Bowel Disease

“…These include restitution, in which local epithelial cells migrate to cover denuded areas, as well as increased mucus production and blood flow, followed by proliferation and differentiation programs. The mucus serves to buffer cells against abrasion by luminal contents and to create a microclimate near the epithelial surface (Halm & Halm, 2000). In colon from guinea pigs with experimental colitis, the depletion of mucus was due to less mucus in goblet cells rather than a decrease in goblet cell number (Kaftan & Wright, 1989).…”

Variational Image Segmentation for Endoscopic Human Colonic Aberrant Crypt Foci

“…By way of illustration, the human eye can distinguish objects with 125 to 165 micron (1 micron is equal to 10 −6 meter), while a high-resolution endoscope can discriminate objects with 10 to 17 micron. To detect details in the colonic mucosa it is necessary to distinguish parts of tissue with 10 micron (for instance, the dimension of a normal human crypt is approximately 74 and 433 micron, respectively, for the horizontal and vertical cross sections, see [19,22]). …”