Pothoulakis C, Galili U, Castagliuolo I, Kelly C P, Nikulasson S, Dudeja P K, Brasitus T A, LaMont J T
Section of Gastroenterology, Evans Memorial Department of Clinical Research, Boston University School of Medicine, Massachusetts, USA.
Gastroenterology. 1996 Jun;110(6):1704-12. doi: 10.1053/gast.1996.v110.pm8964394.
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.
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.
几乎所有人类血清都含有一种免疫球蛋白G抗体（抗半乳糖抗体），该抗体能结合大多数哺乳动物细胞（而非人类细胞）上表达的三糖Galα1-3Galβ1-4GlcNAc。由于啮齿动物体内艰难梭菌毒素A的受体含有这种三糖，本研究旨在探究抗半乳糖抗体是否能模拟毒素A的肠毒素作用并与含有该三糖的受体结合。
将大鼠结肠腔内暴露于纯化的人抗半乳糖抗体、对照免疫球蛋白G、毒素A或缓冲液后，测量液体分泌、[3H]-甘露醇通透性以及大鼠肥大细胞蛋白酶II和前列腺素E2的释放。
毒素A（5微克）和抗半乳糖抗体（250微克）而非对照免疫球蛋白（250微克）刺激结肠液体分泌，导致甘露醇通透性增加和大鼠肥大细胞蛋白酶II释放。抗半乳糖抗体和毒素A，以及程度较轻的对照免疫球蛋白G也刺激前列腺素E2的释放，但只有毒素A会引起大鼠结肠黏膜急性炎症。抗半乳糖抗体和毒素A特异性结合到一类结肠刷状缘受体上，解离常数分别为10^(-6)摩尔/升和5.4×10^(-8)摩尔/升。
当毒素A或人抗半乳糖免疫球蛋白G与带有三糖Galα1-3Galβ1-4GlcNAc的受体结合时，大鼠结肠会出现液体分泌增加、通透性增加和肥大细胞活化。
