A human antibody binds to alpha-galactose receptors and mimics the effects of Clostridium difficile toxin A in rat colon
Autor: | C Pothoulakis, TA Brasitus, Ignazio Castagliuolo, Ciaran P. Kelly, J T LaMont, U Galili, PK Dudeja, S Nikulasson |
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Rok vydání: | 1996 |
Předmět: |
Male
Brush border Colon Bacterial Toxins Clostridium difficile toxin A Receptors Cell Surface medicine.disease_cause Antibodies Dinoprostone Immunoglobulin G Enterotoxins Lectins medicine Animals Humans Secretion Mast Cells Rats Wistar Prostaglandin E2 Receptor Microvilli Hepatology biology Toxin Gastroenterology Metalloendopeptidases Rats Biochemistry biology.protein Plant Lectins Antibody medicine.drug |
Zdroj: | Gastroenterology. 110:1704-1712 |
ISSN: | 0016-5085 |
DOI: | 10.1053/gast.1996.v110.pm8964394 |
Popis: | BACKGROUND & AIMS: Nearly all human sera contain an immunoglobulin G antibody (antigalactose) that binds the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc expressed on cells from most mammals but not humans. Because the Clostridium difficile toxin A receptor in rodents contains this trisaccharide, the aim of this study was to examine whether antigalactose could mimic the enterotoxic effects of toxin A and bind to receptors containing this trisaccharide. METHODS: Fluid secretion, [3H]-mannitol permeability, and release of rat mast cell protease II and prostaglandin E2 were measured after luminal exposure of rat colon to either purified human anti-galactose, control immunoglobulin G, toxin A, or buffer. RESULTS: Toxin A (5 micrograms) and antigalactose (250 micrograms) but not control immunoglobulin (250 micrograms) stimulated colonic fluid secretion and caused increased mannitol permeability and rat mast cell protease II release. Antigalactose and toxin A and, to a lesser degree, control immunoglobulin G also stimulated release of prostaglandin E2, but only toxin A produced acute inflammation of rat colonic mucosa. Antigalactose and toxin A bound specifically to a single class of colonic brush border receptors with dissociation constants of 10(-6) mol/L and 5.4 x 10(-8) mol/L, respectively. CONCLUSIONS: Fluid secretion, increased permeability, and mast cell activation occur in rat colon when toxin A or human antigalactose immunoglobulin G bind to receptors bearing the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc. (Gastroenterology 1996 Jun;110(6):1704-12) |
Databáze: | OpenAIRE |
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