抑制百日咳博德特氏菌黏附于人纤毛呼吸道上皮细胞的受体类似物和单克隆抗体。
Receptor analogs and monoclonal antibodies that inhibit adherence of Bordetella pertussis to human ciliated respiratory epithelial cells.
作者信息
Tuomanen E, Towbin H, Rosenfelder G, Braun D, Larson G, Hansson G C, Hill R
机构信息
Laboratory of Microbiology, Rockefeller University, New York, New York 10021.
出版信息
J Exp Med. 1988 Jul 1;168(1):267-77. doi: 10.1084/jem.168.1.267.
The adherence of Bordetella pertussis to human respiratory cilia is critical to the pathogenesis of whooping cough. To explore the development of agents that could interrupt adherence, the structure of the receptor on the ciliary surface was investigated. Using an in vitro adherence assay to human ciliated epithelial cells, galactose, lactose, and complex carbohydrates containing lactose eliminated adherence when preincubated with the bacteria. 10(-2) M galactose eluted adherent bacteria from cilia. B. pertussis and its two purified adhesins bound specifically to natural lactose-containing glycolipids in a TLC assay. mAbs to eukaryotic glycoconjugates with specificity for substituted galactose-glucose moieties blocked adherence when preincubated with ciliated cells. The carbohydrates that serve as receptors for B. pertussis on human cilia are galactose-glucose-containing glycolipids. Receptor analogs and anti-receptor antibodies effectively block adherence of B. pertussis to cilia and thus should be considered candidates for therapeutic intervention against disease.
百日咳博德特氏菌对人呼吸道纤毛的黏附对于百日咳的发病机制至关重要。为了探索能够阻断黏附的药物的研发，对纤毛表面受体的结构进行了研究。使用针对人纤毛上皮细胞的体外黏附试验，半乳糖、乳糖以及含乳糖的复合碳水化合物在与细菌预孵育时可消除黏附。10⁻² M半乳糖可从纤毛上洗脱黏附的细菌。在薄层层析试验中，百日咳博德特氏菌及其两种纯化的黏附素与天然含乳糖糖脂特异性结合。对具有取代半乳糖 - 葡萄糖部分特异性的真核糖缀合物的单克隆抗体在与纤毛细胞预孵育时可阻断黏附。在人纤毛上作为百日咳博德特氏菌受体的碳水化合物是含半乳糖 - 葡萄糖的糖脂。受体类似物和抗受体抗体可有效阻断百日咳博德特氏菌对纤毛的黏附，因此应被视为针对该疾病进行治疗干预的候选药物。
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