多粘菌素B单克隆抗体对细菌内毒素的拮抗作用

Anti-polymyxin B Monoclonal Antibodies Protect Mice Against Lipopolysaccharide Lethality

Clone45为IgM类抗多粘菌素B（PMB）单克隆抗体。ELISA抑制试验表明，Clone45与一系列光滑型和粗糙型细菌脂多糖（LPS）以及类脂A能在体外竞争与PMB结合，而与不含类脂A组分的脑膜炎球菌荚膜多糖及合无内毒素活性的类脂A组分的Rh．viridis脂多糖不发生竞争。在盐酸半乳糖致敏的及非致敏的小鼠内毒素休克模型，提前30-120min静脉注射Clone45对随后的致死性内毒素（光滑型E．coliO55：BS和粗糙型S．minnesotaR595LPS）攻击的小鼠具有显著保护作用。Clone45预处理可显著降低LPS诱导的血请肿瘤坏死因子（TNF）水平。这些结果提示，Clone45具有模拟类脂A的表面抗原结构，可作为类脂A的替身和LPS的受体拮抗剂，阻断内毒素诱生炎症介质的致病环节，起到抗内毒素休克的作用。

Clone 45 is an IgM monoclonal antibody directed against polymyxin B(PMB). A vanely of smooth-typedand rough-typed lipololysacchrides (LPS),and lipid A, rather than a capsular polysaccharide from N. meningitidis (whthout lipid A protion) and LPS isolated from Rhodopseudomonas viridis (with non-toxic lipid Aprotion),were found to be able to inhibit the binding of Clone 45 to PMB in ELISA. Administration of Clone 4530-120min prior to LPS injection protected D-galactosamine-sensitized or non-sensitized mice against lethalchallenge of E.colt O55: B5 and S. minnesota R595 LPS and reduced TNFα production. These observations indicate that Clone 45 may have the surface antigenic structure mimicking lipid A .and that Clone 45 may act as lipidA surrogate and LPS receptor antagonist so as to inhibit the production of cytokines (TNF,etc. )responsible forendotoxin shock and thus protect the animals from lethal endotoxemia.