Castagliuolo I, LaMont J T, Qiu B, Nikulasson S T, Pothoulakis C
Division of Gastroenterology, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Gastroenterology. 1996 Aug;111(2):433-8. doi: 10.1053/gast.1996.v111.pm8690209.
BACKGROUND & AIMS: Clostridium difficile toxin A causes secretion and intestinal inflammation in rodents by binding to a specific trisaccharide Gal alpha 1-3Gal beta 1-4 GlcNAc on enterocyte receptors. The purpose of this study was to explore the ability of Synsorb 90 (Synsorb Biotech Inc., Calgary, Alberta, Canada), and inert support carrying this trisaccharide, to bind toxin A in vitro and to inhibit its enterotoxic effects in vivo.
Binding of [3H]toxin A to Synsorb 90, Synsorb 83 (beta-mannose attached), and Chromosorb P (inert support with no sugar attached) (Synsorb Biotech Inc.) was measured. The inhibitory effects of these compounds on toxin A-mediated fluid secretion, mannitol permeability, and histological damage were measured in ileal loops in vivo.
Toxin A showed specific binding to Synsorb 90, bearing the specific trisaccharide that binds toxin A, but not to Synsorb 83 or to Chromosorb P. Pretreatment of rats with Synsorb 90 by gavage (200 mg/kg body wt), but no Synsorb 83 or Chromosorb P at the same doses, dramatically reduced toxin A-associated fluid secretion and permeability.
An immobilized toxin A receptor sequesters toxin A in the intestinal lumen and inhibits its effects of ileal mucosa. These results suggest a potential use for this agent in treating patients with C. difficile colitis.
艰难梭菌毒素A通过与肠上皮细胞受体上的特定三糖Galα1-3Galβ1-4GlcNAc结合，在啮齿动物中引起分泌和肠道炎症。本研究的目的是探讨Synsorb 90（加拿大阿尔伯塔省卡尔加里的Synsorb生物技术公司），一种携带这种三糖的惰性载体，在体外结合毒素A以及在体内抑制其肠毒素作用的能力。
测定[3H]毒素A与Synsorb 90、Synsorb 83（连接有β-甘露糖）和Chromosorb P（未连接糖的惰性载体）（Synsorb生物技术公司）的结合情况。在体内回肠袢中测定这些化合物对毒素A介导的液体分泌、甘露醇通透性和组织学损伤的抑制作用。
毒素A显示出与携带能结合毒素A的特定三糖的Synsorb 90特异性结合，但不与Synsorb 83或Chromosorb P结合。通过灌胃给大鼠预处理Synsorb 90（200mg/kg体重），但相同剂量的Synsorb 83或Chromosorb P则无此效果，这显著降低了与毒素A相关的液体分泌和通透性。
固定化的毒素A受体在肠腔内隔离毒素A并抑制其对回肠黏膜的作用。这些结果表明该制剂在治疗艰难梭菌结肠炎患者方面具有潜在用途。
