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Bacterial endotoxin: molecular relationships of structure to activity and function
Author(s) -
Rietschel Ernst T.,
Kirikae Teruo,
Schade F. Ulrich,
Mamat Uwe,
Schmidt Günter,
Loppnow Harald,
Ulmer Artur J.,
Zähringer Ulrich,
Seydel Ulrich,
Di Padova Franco,
Schreier Max,
Brade Helmut
Publication year - 1994
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.8.2.8119492
Subject(s) - lipid a , lipopolysaccharide , chemistry , oligosaccharide , monoclonal antibody , tumor necrosis factor alpha , biochemistry , biological activity , lipid metabolism , function (biology) , glycolipid , epitope , microbiology and biotechnology , antibody , biology , in vitro , immunology
Endotoxins of Gram‐negative microbes fulfill as components of the outer membrane a vital function for bacterial viability and, if set free, induce in mammalians potent pathophysiological effects. Chemically, they are lipopolysaccharides (LPS) consisting of an O‐specific chain, a core oligosaccharide, and a lipid component, termed lipid A. The latter determines the endotoxic activities and, together with the core constituent Kdo, essential functions for bacteria. The primary structure of lipid A of various bacterial origin has been elucidated and lipid A of Escherichia coli has been chemically synthesized. The biological analysis of synthetic lipid A partial structures proved that the expression of endotoxic activity depends on a unique primary structure and a peculiar endotoxic conformation. The biological lipid A effects are mediated by macrophage‐derived bioactive peptides such as tumor necrosis factor α (TNF). Macrophages possess LPS receptors, and the lipid A regions involved in specific binding and cell activation have been characterized. Synthetic lipid A partial structures compete the specific binding of LPS or lipid A and antagonistically inhibit the production of LPS‐induced TNF. LPS toxicity, in general, and the ability of LPS to induce TNF are also suppressed by a recently developed monoclonal antibody (IgG2a), which is directed against an epitope located in the core oligosaccharide. At present we determine molecular and submolecular details of the specificity of the interaction of lipid A with responsive host cells with the ultimate aim to provide pharmacological or immunological therapeutics that reduce or abolish the fatal inflammatory consequences of endotoxicosis.—Rietschel, E. Th., Kirikae, T., Schade, F. U., Mamat, U., Schmidt, G., Loppnow, H., Ulmer, A. J., Zähringer, U., Seydel, U., Di Padova, F., Schreier, M., Brade, H. Bacterial endotoxin: molecular relationships of structure to activity and function. FASEB J. 8: 217‐225; 1994.