Endotoxins biological activity

E. Th. Rietschel, L. Brade, U. F. Schade, U. Seydel, U. Zahringer, S. Kusumoto, and H. Brade, in E. Schrinner, M. Richmond, G. Seibert, and U. Schwartz (Eds.), Sutface Structures of Microorganisms and Their Interaction with the Mammalian Host Bacterial Endotoxins Properties and Structure of Biologically Active Domains, p. 1. Verlag Chemie, Weinheim, 1988. 

U. Seydel and K, Brandenburg, in A. Nowotny, J. I. Spitzer, and E. J. Ziegler (Eds.), Endotoxin Research Series, Vol. 1, Cellular and Molecular Aspects of Endotoxin Reactions Conformations of Endotoxin and Their Relationship to Biological Activity, p. 61. Excerpta Medica, Elsevier, Amsterdam, 1990. 

Endotoxin. Endotoxin is the lipopolysaccharide that comprises a major portion of the cell wall of the gram-negative bacteria. The endotoxins from each species of bacteria are different but the lipid A moiety is similar for the Enterobacterlaceae, and has a similar series of biological actions regardless of its source. The lipid A material is different in some of the gram-negative rods present in cotton (i.e. in the Pseudomonas species). This variety of compounds makes quantitation of endotoxin difficult. Hence, it is usually measured by its biological activity as compared to a standard endotoxin (usually that of E. coll). (See Table VIII.)... 

A link between bacteria and tumor therapy was found early, at the beginning of the XVIII century [10]. By the end of the XIX century, Coley [11] developed a treatment for cancer with a mixture of bacterial toxins. In 1943 Shear and Turner [4] found that the antitumor effect of Coley s toxin was due to endotoxins, and after several decades it was shown that the biological activity of LPS was due to the lipid A [5]. We investigated the structures of lipids A with regard to their antitumor activities [12], finding that the optimum in vivo activity is obtained with diglucosamines acylated by 3 long chain fatty acids. 

While these compounds may be useful as reference compounds for structural analysis of endotoxins and helpful for orienting investigations aiming at the establishment of the chemical structure/biological activity relationship of these substances, they are still far from representing any Lipid A fragment and even less the hydrophobic region of an endotoxin. From... 

H. Paulsen Synthesis of amino- and branched chain mono- and oligosaccharides L. Szabo Structural features and biological activity of the Bordella pertussis endotoxin... 

Suda, Y., Kim, Y.M., Ogawa, T., Yasui, N., Hasegawa, Y., Kashihara, W., Shimoyama, T., Aoyama, K., Nagata, K., Tamura, T., Kusumoto, S. Chemical structure and biological activity of a lipid A component from Helicobacter pylori strain 206. J Endotoxin Res 7 (2001) 95-104. 

Mueller, M., Lindner, B., Kusumoto, S., Fukase, K., Schromm, A.B., Seydel, U. Aggregates are the biologically active units of endotoxin. J Biol Chem 279 (2004) 26307-26313. 

Rietschel, E.Th., Galanos, C., Tanaka, A., Ruschmann, E., Ltideritz, O., Westphal O. Biological activities of chemically modified endotoxins. Eur J Biochem 22 (1971) 218-224. 

Kaczynski, Z., Braun, S., Lindner, B., Niehaus, K., Holst, O. Investigation ofthe chemical structure and biological activity of oligosaccharides isolated from rough-type Xanthomonas campestris pv. campestris B100 lipopolysaccharides. J Endotoxin Res 13 (2007) 101-108. 

Frecer, V., Ho, B., Ding, J.L. Interpretation of biological activity data of bacterial endotoxins by simple molecular models of mechanism of action. Eur J Biochem 267 (2000b) 837-52. 

Raetz, C.R.H., Brozek, K.A., Clementz, T., Coleman, J.D., Galloway, S.M., Golenbock, D.T., Hampton, R. Y. Gram-negative endotoxin a biologically active lipid. Cold Spring Harbor Symp. Quant Biol 53 (1988) 973-982. 

Erridge, C., Stewart, J., Bennett-Guerrero E, McIntosh TJ, Poxton, I.R. The biological activity of a liposomal complete core LPS vaccine. J Endotoxin Res 8 (2002) 39 16. 

Biological purity As chemically synthesized products are totally nonbiological in origin, thus there is no chance of contamination with fMLP-related peptides, endotoxin or other biologically active molecules that could affect bioactivity. 

A partially purified Bacillus thurlnglensis var. israelensls (Bti) 6-endotoxin was used to Immunize rabbits. The antisera obtained have an improved specificity towards the mosquito larvacidal activity of the toxin, as opposed to antiserum raised when the whole crystal was used as immunogen. Using a two step/indirect ELISA (enzyme linked immunosorbent assay) procedure developed in our laboratory, fourteen experimental formulations were tested, and the results were compared with bioassays. An average of 69.1 international units 20% c.v. was found to associate with each ug of toxin detected by the ELISA. Our data indicate that when toxin specific antisera are available, Immunoassays can be used to predict the biological activity of Bti samples with reasonable accuracy. 

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