In vivo induction of gliadin-mediated enterocyte damage in rats by the mannosidase inhibitor, swainsonine: a possible animal model for celiac disease.
Simultaneous feeding of gliadin and swainsonine, an inhibitor of alpha-D-mannosidases, in rats disturbed enterocytic maturation as shown by a marked loss of activities of alkaline phosphatase and gamma-glutamyltransferase. Morphologically, simultaneous treatment with gliadin and swainsonine caused destruction and decreased density of microvilli, as shown by electron microscopy. Neither gliadin nor swainsonine when given alone had significant effects on enterocytic enzyme activities or enterocytic morphology. Binding of enterocytic glycoproteins to both gliadin-Sepharose and concanavalin A-Sepharose was significantly increased in rats treated with swainsonine. Because swainsonine causes the formation of hybrid-type oligosaccharides with a high binding affinity to mannose-specific lectins, the observed alterations of enterocytic maturation and morphology are presumably caused by the increased binding of gliadin to enterocytic glycoproteins. A possible analogy in the etiology of celiac disease is discussed.
D000469:Alkaline Phosphatase / Q000378:metabolism; D000470:Alkaloids; D000818:Animals; D002446:Celiac Disease / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D003208:Concanavalin A / Q000378:metabolism; D004195:Disease Models, Animal; D005903:Gliadin / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D007421:Intestine, Small / Q000201:enzymology / Q000648:ultrastructure*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008361:Mannosidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008871:Microvilli / Q000648:ultrastructure; D010940:Plant Proteins / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012685:Sepharose / Q000378:metabolism; D017026:Swainsonine
D000470:Alkaloids; D006023:Glycoproteins; D010940:Plant Proteins; D003208:Concanavalin A; D005903:Gliadin; D012685:Sepharose; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase; D008361:Mannosidases; D017026:Swainsonine