2006 Fiscal Year Final Research Report Summary
Function of gastro-intestinal mucin-derived acidic oligosaccharaides recognized by anti-mucin monoclonal antibodies
| Project/Area Number |
16590629
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kitasato University |
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Principal Investigator |
ISHIHARA Kazuhiko Kitasato University, School of Allied Health Sciences, Professor, 医療衛生学部, 教授 (10104530)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Takeshi Kitasato University, School of Medicine, Lecturer, 医学部, 講師 (30050652)
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| Project Period (FY) |
2004 – 2006
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| Keywords | gastro-intestinal tract / mucin / mucosal damage / acidic oligosaccharide |
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| Research Abstract |
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
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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
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Research Products
(14 results)
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[Journal Article] An anti-mucin monoclonal antibody, PGM34, against 6-sulfated blood-group H type 2 antigen on the carbohydrate moiety of mucin : Analysis of the epitope sequence and immunohistochemica 1 study.2007
Author(s)
Tsubokawa D, Goso Y, Sawaguchi A, Kurihara M, Ichikawa T, Sato N, Suganuma T, Hotta K, Ishihara K.
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Journal Title
FEBS Journal 274
Pages: 1833-1848
Description
「研究成果報告書概要(欧文)」より
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[Book] 胃粘液バリアー2004
Author(s)
堀田恭子, 石原和彦
Total Pages
123
Publisher
メジカルビュー
Description
「研究成果報告書概要(和文)」より
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