Mucus hypersecretion in the gallbladder epithelium of ground squirrels fed a lithogenic diet for the induction of cholesterol gallstones

Abstract

This study identified mucus granules, determined mode of release and quantified their volume in the gallbladder epithelium of Richardson's ground squirrels (Spermophilus richardsonii) fed a lithogenic diet of 2% cholesterol to experimentally induce gallstone formation. Tissue was examined using light microscopy histochemistry, scanning and transmission electron microscopy, as well as autoradiography and morphometry at the electron microscopic level. Autoradiography demonstrated incorporation of a glycoprotein precursor, [3H]galactose, within the membrane-bound granules localized in the supranuclear region of the epithelial cells. Exocytosis of granule contents was by merocrine secretion. Morphometry indicated a significant increase in the amount of intracellular mucin granules as early as 18 hr on the lithogenic diet, a feature that continued throughout the experimental period of 20 weeks. Mucus synthesis/secretion rates returned to control values within 3 weeks after removal from the diet. Scanning electron microscopy observations revealed a thick sludge-like layer overlying the epithelium at a time in the chronology of the cholelithiasic model that correlated well with the initial phases of stone formation. Histochemistry showed this layer to be a mixture of acidic mucins. Neutral mucins were not observed. The hypersecretion of mucus and formation of this sludge-like layer appear to be critical nucleating factors in the formation of cholesterol gallstones.

Characterization of glycoproteins in the epithelial cells of human and other mammalian gallbladder: A review

“…Moreover, the enhancement of mucus secretion and an increase in mitosis before the formation of any precipitate have been described (Freston et al, 1969;Lee and Scott, 1982;Lee et al, 1981b;Pemsingh et al, 1987b;Putz and Willems, 1981;Scott, 1976). By using 3 H-glucosamine, Malet et al (1989) demonstrated that, in animals fed with a cholesterol-rich diet, mucin production increases twofold and sevenfold after 1 and 3 weeks, respectively.…”

A histopathological and histochemical study of cholecystitis

“…The implication of mucin in gallstone formation has been widely studied. Hypersecretion of mucus occurs during gallstone formation in humans [6][7][8][9] and experimental animals [10]. Apart from forming the nucleus for calculus, the mucins form a structural component of gallstones as shown by histochemical studies on calculi [11,12].…”

Targeted disruption of the murine mucin gene 1 decreases susceptibility to cholesterol gallstone formation

“…Indeed, hypersecretion of gallbladder mucins is a prerequisite for gallstone formation, and increased amounts of gallbladder mucins are consistently observed in gallbladder bile of several animal models of gallstones (7)(8)(9). Also, mucins are found within cholesterol gallstones, where they act as a matrix for stone growth (10).…”