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The FASEB Journal, Vol 5, 2652-2660, Copyright © 1991 by The Federation of American Societies for Experimental Biology

REVIEWS

Gram-negative endotoxin: an extraordinary lipid with profound effects on eukaryotic signal transduction

CR Raetz, RJ Ulevitch, SD Wright, CH Sibley, A Ding and CF Nathan
Department of Biochemistry, Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065.

The lipid A domain of lipopolysaccharide (LPS) is a unique, glucosamine- based phospholipid that makes up the outer monolayer of the outer membrane of most gram-negative bacteria. Because of its profound pharmacological effects on animal cells, especially those of the immune system, lipid A is also known as endotoxin. Despite decades of earlier work, the precise chemistry of endotoxins and the biochemical pathways for their enzymatic synthesis have been elucidated only within the past 5 years. In this review, we summarize the essentials of endotoxin biochemistry and also present recent experiments aimed at identifying surface receptors, signal-transducing elements, transcriptional factors, and key intracellular targets involved in the response of animal cells to endotoxins.


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