Function of gastro-intestinal mucin-derived acidic oligosaccharaides recognized by anti-mucin monoclonal antibodies

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We developed a monoclonal antibody, designated PGM34, by immunizing a mouse with purified pig gastric mucin. PGM34 recognized the carbohydrate portion of the mucins. Oligosaccharide-alditols obtained from the pig gastric mucin were fractionated by successive gel-filtration, ion-exchange, and normal phase high-performance liquid chromatography, and tested for the reactivity with PGM34. Two purified oligosaccharide-alditols reacting with PGM34 were obtained and their structures were determined by nuclear magnetic resonance spectroscopy as Fucα1-2Galβ1-4GlcNAc(6SO_3H)β1-6(Fucα1-2Galβ1-3)GalNAc-ol and Fucα1-2-Galβ1-4GlcNAc (6SO_3H) β1-6 (Galβ1-3)Gal-NAc-ol. None of the defucosylated or desulfated form of these oligosaccharides reacted with PGM34. Thus, the epitope of PGM34 was determined as the Fucα1-2Galβ1-4GlcNAc (6SO_3H)β-sequence. Immunohistochemical observations of rat gastrointestinal tracts showed that PGM34 stained the surface mucous cells close to the generative cell zone in the g … More astric fundus and the goblet cells in the small intestine, but only slightly stained the antral mucous cells in the stomach. These data, taken together, showed that PGM34 is a very useful tool to reveal the role of mucins having characteristic sulfated oligosaccharides.To investigate the antineoplastic chemotherapy-induced small intestinal injury, 5-fluorouracil(5-FU) was orally administered to rats for 5 days. The 5-FU treatment caused a significant decrease in the number of mucus cells in the small intestine observed by an immunohistochemical method using PGM34. This reduction of mucus cells was significantly inhibited by the co-administration of lafutidine, a novel H2-blocker, but not by cimetidine, an H2-blocker of the first generation. The mucin content in the small intestine significantly decreased in the 5-FU treated group. This reduction was significantly recovered by the co-administration of lafutidine. These results support the efficacy of lafutidine toward 5-FU-induced mucositis in rat small intestine. Less