Protective antibody to endotoxin core: the emperor's new clothes?
Protective antibody to endotoxin core: the emperor's new clothes?
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内毒素核心保护性抗体：皇帝的新衣？
DOI：
10.1093/infdis/158.2.286
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Ziegler,EJ
中科院分区：
文献类型：
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作者：
Ziegler,EJ
很久很久以前，在安徒生最受欢迎的一个故事里，住着一个既虚荣又容易上当受骗的皇帝。出于对自己声誉的担忧，他暂时自欺欺人，并把他的大多数臣民沿着一起拖走。有一天，他穿着新衣服游行，他开始发抖，最后他不得不接受一个孩子提出的可能性，即他备受赞赏的服装不是真实的。类似的担忧也困扰着研究人员，他们报告说，将抗血清被动转移到寡糖缺陷型（粗糙型）内毒素突变体上，可以保护其免受光滑革兰氏阴性菌及其内毒素（脂多糖[LPS]）的攻击。内毒素能够引发许多与革兰氏阴性菌血症死亡相关的生化异常。虽然需要抗生素来清除菌血症，但它们不能逆转休克的发展，因为血液中游离的内毒素或暴露在循环细菌表面的内毒素会继续激活细胞损伤的介质，直到宿主的自然清除和解毒机制能够处理负荷。因此，革兰氏阴性休克的免疫干预策略一直集中在LPS分子，特别是其核心决定因素上。与类型特异性寡糖侧链（O抗原）不同，内毒素核心结构（核心糖和脂质A）似乎在对人类致病的广泛革兰氏阴性属中高度保守。人们认为，这些共同的决定因素可能会刺激广泛的交叉反应抗体的LPS，可以发挥作用，以加强自然宿主的防御和/或减少生物学
Once upon a time, in one of Hans Christian Andersen's best-loved tales, there lived an emperor as gullible as he was vain. Out of fear for his reputation he engaged in temporary self-deception and dragged most of his subjects along with him. On parade one day in some new clothes, he began to shiver, and he finally was forced to accept the possibility, suggested by a child, that his much-admired costume was not real. Similar worries have plagued investigators who report that passive transfer of antisera to oligosaccharide-deficient (rough) endotoxin mutants results in protection against challenge with smooth gramnegative bacteria and their endotoxins (lipopolysac-charides [LPS]).The rationale for research on antibodies to en-dotoxin core is straightforward and can be summa-rized simply in the following set of hypotheses. Endotoxin is capable of initiating many of the bio-chemical abnormalities associated with death from gram-negative bacteremia. Although antibiotics are required to clear bacteremia, they do not reverse evolving shock, because endotoxin free in the bloodstream or exposed on the surface of circulating bacteria continues to activate mediators of cell damage until natural clearance and detoxification mechanisms in the host are able to handle the load. There-fore, strategies for immunologic intervention in gram-negative shock have been focused on the LPS molecule and on its core determinants in particular. Unlike the type-specific oligosaccharide side chains (O antigens), endotoxin core structures (core sugars and lipid A) seem highly conserved over the wide range of gram-negative genera pathogenic for hu-mans. It was thought that these common deter-minants might stimulate widely cross-reactive anti-bodies to LPS that could function to augment natural host defenses and/or decrease biologically