A human antibody binds to alpha-galactose receptors and mimics the effects of Clostridium difficile toxin A in rat colon

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 110; no. 6; p. 1704
• Main Authors: Pothoulakis, C, Galili, U, Castagliuolo, I, Kelly, C P, Nikulasson, S, Dudeja, P K, Brasitus, T A, LaMont, J T
• Format: Journal Article
• Language: English
• Published: United States 01.06.1996
• Subjects: Animals; Antibodies - immunology; Bacterial Toxins - pharmacology; Colon - drug effects; Colon - immunology; Colon - metabolism; Dinoprostone - biosynthesis; Enterotoxins - pharmacology; Humans; Lectins - metabolism; Lectins - pharmacology; Male; Mast Cells - enzymology; Metalloendopeptidases - biosynthesis; Microvilli - immunology; Microvilli - metabolism; Plant Lectins; Rats; Rats, Wistar; Receptors, Cell Surface - immunology
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1053/gast.1996.v110.pm8964394

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. 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. 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. 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.