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[细菌内毒素:化学结构与生物学效应之间的关系]

[Bacterial endotoxins: relationship between chemical structure and biological effect].

作者信息

Rietschel E T, Brade L, Schade F U, Seydel U, Zähringer U, Mamat U, Schmidt G, Ulmer A J, Loppnow H, Flad H D

机构信息

Institut für Experimentelle Biologie und Medizin, Forschungsinstitut Borstel.

出版信息

Immun Infekt. 1993 Apr;21(2):26-35.

PMID:8340135
Abstract

Gram-negative bacteria carry on their surface endotoxins, which are essential for bacterial growth and survival. If released from the bacterial cell, endotoxins induce in higher organisms a great variety of pathophysiological effects. Chemically, endotoxins constitute lipopolysaccharides (LPS), the lipid component (termed lipid A) of which is responsible for the induction of endotoxin effects. The structural and conformational parameters, endowing lipid A with its potent bioactivity, have been well characterized. The toxic effects of endotoxins are initiated by the specific interaction of lipid A with macrophages/monocytes resulting in the production of peptide or lipid mediators. This interaction is governed by a unique (toxic) conformation of lipid A on the one hand, and by specific cellular receptors on the other. The interaction and subsequent mediator production can be specifically and antagonistically inhibited by lipid A partial structures. A recently developed monoclonal anti-LPS-antibody cross-reacts with endotoxins of various bacterial origin, and it cross-protects against harmful endotoxin effects such as pyrogenicity and lethality.

摘要

革兰氏阴性菌在其表面携带内毒素,内毒素对细菌的生长和存活至关重要。如果内毒素从细菌细胞中释放出来,它会在高等生物中引发各种各样的病理生理效应。从化学角度来看,内毒素由脂多糖(LPS)组成,其中的脂质成分(称为脂质A)负责引发内毒素效应。赋予脂质A强大生物活性的结构和构象参数已得到充分表征。内毒素的毒性作用是由脂质A与巨噬细胞/单核细胞的特异性相互作用引发的,从而导致肽或脂质介质的产生。这种相互作用一方面由脂质A独特的(毒性)构象决定,另一方面由特定的细胞受体决定。脂质A的部分结构可以特异性地、拮抗地抑制这种相互作用以及随后的介质产生。最近开发的一种单克隆抗LPS抗体与各种细菌来源的内毒素发生交叉反应,并能交叉保护机体免受诸如致热和致死等有害内毒素效应的影响。

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