Lipopolysaccharide:: Structure, bioactivity, receptors, and signal transduction

Endotoxin is the major component of the outer leaflet of Gram-negative bacteria and expresses profound immunstimulatory and inflammatory capacity. The past years have provided new insights into the chemistry and biology of the endotoxin molecule. The knowledge about the submolecular structure of endotoxin, the synthesis of lipid A analogs and the development of endotoxin antagonists have provided an enormous body of information about the process of cellular activation by endotoxin. Furthermore, there was much progress in the knowledge concerning the interplay between endotoxin and soluble or cellular receptors, the signal transduction pathways which are activated by endotoxin, and the cellular responses to endotoxin. However, the precise mechanisms of endotoxin activity in the host turned out to be extremely complex and remain to be completely understood. Nevertheless, the latest advances in understanding the activation of monocytes/macrophages by LPS certainly provide the basis for the future development of novel and hopefully better strategies in the fight against Gram-negative infections.