A case for an endotoxic conformation.
Gram-negative bacteria express on their surface endotoxins which are essential for bacterial growth and survival. If released from the bacterial cell, endotoxins induce, in higher organisms, a variety of pathophysiological effects known as manifestations of bacterial sepsis. Chemically, endotoxins are lipopolysaccharides (LPS) composed of a polysaccharide and a lipid component, termed lipid A, which is responsible for the induction of endotoxin effects. Lipid A of all endotoxically active LPS have a similar architecture. The structural and conformational parameters endowing lipid A with its potent bioactivity have been well characterized. The toxic effects of endotoxins or their lipid A component, respectively, are initiated by the specific interaction of lipid A with macrophages/monocytes resulting in the production of peptide or lipid mediators like tumor necrosis factor alpha (TNF), the leukotrienes, and oxygen radicals. This interaction requires a unique "endotoxic conformation" of lipid A on the one hand, and specific cellular receptors on the other. The interaction and subsequent mediator production can be specifically and antagonistically inhibited by lipid A partial structures.
Forschungsinstitut Borstel, Institut für Experimentelle Biologie und Medizin, Germany.
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Seydel
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Brandenburg
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Rietschel
D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D004731:Endotoxins / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008050:Lipid A / Q000737:chemistry / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology; D008969:Molecular Sequence Data; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D004731:Endotoxins; D008050:Lipid A; D008070:Lipopolysaccharides