Endotoxin molecular structure

Leone, S., Silipo, A., Nazarenko, E., Lanzetta, R., Parrilli, M., Molinaro, A. Molecular structure of endotoxins from Gram-negative marine bacteria an update. Mar Drugs 5(3) (2007b), 85-112. 

Figure 1 Molecular structure of Bacillus thuringienses delta endotoxin. (Reproduced from Li J, Carroll J, and Ellar DJ (1991) Nature 353 815-821, with permission of the Nature Publishing Group.)...

Rietschel ET, Kirikae T, Schade FU et al (1994) Bacterial endotoxin molecular relationships of structure to activity and function. FASEB J 8 217-225... 

P. Stutz, H. Aschauer, J. Hildebrandt, C. Lam, H. Loibner, I. Macher, D. Scholz, E. Schiltze, and H. Vyplel, in A. Nowotny (Ed.), Endotoxin Research Series, Vol. 1, Cellular and Molecular Aspects of Endotoxin Reactions Chemical Synthesis of Endotoxin Analogs and Some Structure Activity Relationships, p. 129. Elsevier, Amsterdam, 1990. 

Although H. pylori induces chronic infection whereas C. jejuni induces an acute infection (and to which the structural characteristics and biological properties of endotoxin, particularly their lipid A components contribute), both bacteria induce pathogenic autoimmune responses in which molecular mimicry in the... 

Moran, A.P., Appelmelk, B.J., Aspinall, G.O. Molecular mimicry of host structures by lipopolysaccharides of Campylobacter and Helicobacter spp. implications in pathogenesis. J Endotoxin Res 3 (1996) 521-531. 

Adsorbents are used in medicine mainly for the treatment of acute poisoning, whereas other extracorporeal techniques based on physico-chemical principles, such as dialysis and ultrafiltration, currently have much wider clinical applications [1]. Nevertheless, there are medical conditions, such as acute inflammation, hepatic and multi-organ failure and sepsis, for which mortality rates have not improved in the last forty years. These conditions are usually associated with the presence of endotoxin - lipopolysaccharide (LPS) or inflammatory cytokines - molecules of peptide/protein nature [2]. Advantages of adsorption over other extracorporeal techniques include ability to adsorb high molecular mass (HMM) metabolites and toxins. Conventional adsorbents, however, have poor biocompatibility. They are used coated with a semipermeable membrane of a more biocompatible material to allow for a direct contact with blood. Respectively, ability of coated adsorbents to remove HMM solutes is dramatically reduced. In this paper, preliminary results on adsorption of LPS and one of the most common inflammatory cytokines, TNF-a, on uncoated porous polymers and activated carbons, are presented. The aim of this work is to estimate the potential of extracorporeal adsorption technique to remove these substances and to relate it to the porous structure of adsorbents. 

In a typical aqueous environment that contains small amounts of divalent cations, endotoxin has a molecular weight of about 10 Da (21). If divalent cations are removed from the aqueous environment by chelators, the endotoxin bilayers break down into micelles of 300,000 to 1,000,000 molecular weight. When these micelles are further broken down in the presence of surface-active agents, their molecular weight drops again to about 10,000-20,000. However, these steps are completely reversible if the detergents are dialyzed out, and divalent cations are added back to the endotoxin, the micelles and then the membranous structures reassemble themselves. ... 

The toxicity of polycarboxylic acid polymers is more sensitive to polymer structure and molecular weight than antitumor activity. The acute toxicity is markedly decreased with decreasing molecular weight (Table VI and XI). Further,polyanion polymers have been shown to highly sensitize mice to bacterial endotoxin (39)> this activity is strikingly molecular weight dependent as shown in Tables VII and XI as well as dose dependent ( 3. The enhanced sensitivity to endotoxin by synthetic anionic polymers has been extensively studied, but the mechanism of action is still not understood (39)-... 

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