A human antibody binds to alpha-galactose receptors and mimics the effects of Clostridium difficile toxin A in rat colon.
OBJECTIVE
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.
Pothoulakis
C
C
Section of Gastroenterology, Evans Memorial Department of Clinical Research, Boston University School of Medicine, Massachusetts, USA.
Galili
U
U
Castagliuolo
I
I
Kelly
C P
CP
Nikulasson
S
S
Dudeja
P K
PK
Brasitus
T A
TA
LaMont
J T
JT
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001427:Bacterial Toxins / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D004768:Enterotoxins / Q000494:pharmacology*; D006801:Humans; D037102:Lectins / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000201:enzymology; D008666:Metalloendopeptidases / Q000096:biosynthesis; D008871:Microvilli / Q000276:immunology / Q000378:metabolism; D037121:Plant Lectins; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000276:immunology*
D000906:Antibodies; D001427:Bacterial Toxins; D004768:Enterotoxins; C045475:Griffonia simplicifolia lectins; D037102:Lectins; D037121:Plant Lectins; D011956:Receptors, Cell Surface; C039707:galactose receptor; C041348:tcdA protein, Clostridium difficile; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus; D015232:Dinoprostone