This paper concerns the potential use of compounds, including lipid A, chitosan, and carrageenan, from marine sources as agents for treating endotoxemic complications from Gram-negative infections, such as sepsis and endotoxic shock. Lipid A, which can be isolated from various species of marine bacteria, is a potential antagonist of bacterial endotoxins (lipopolysaccharide (LPSs)). Chitosan is a widespread marine polysaccharide that is derived from chitin, the major component of crustacean shells. The potential of chitosan as an LPS-binding and endotoxin-neutralizing agent is also examined in this paper, including a discussion on the generation of hydrophobic chitosan derivatives to increase the binding affinity of chitosan to LPS. In addition, the ability of carrageenan, which is the polysaccharide of red alga, to decrease the toxicity of LPS is discussed. We also review data obtained using animal models that demonstrate the potency of carrageenan and chitosan as antiendotoxin agents.

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Some endotoxic properties of lipopolysaccharides (LPS) and lipids A (LA) from the marine bacteria Marinomonas communis ATCC 27118(T), Marinomonas mediterranea ATCC 700492(T), and Chryseobacterium indoltheticum CIP 103168(T) were studied. The preparations tested were shown to have high 50% lethal doses (4 microg per mouse for LPS from M. mediterranea and more than 12 microg per mouse for two other LPS and LA from C. indoltheticum) and were moderate (371 +/- 37 pg/ml at 10 microg/ml of C. indoltheticum LPS), weak (148 +/- 5 pg/ml at 1 microg/ml of M. mediterranea LPS), and zero (LA and LPS from M. communis and LA from C. indoltheticum) inducers of tumor necrosis factor alpha (TNF-alpha) release from peripheral human blood cells. The capacity of the LA and LPS samples from marine bacteria to inhibit TNF-alpha release induced by LPS from Escherichia coli O55 : B5 (10 ng/ml) was also studied.

The chemical structure of a novel lipid A, the major component of the lipopolysaccharide from the marine gammaproteobacterium Marinomonas vaga ATCC 27119 T , was determined by compositional analysis, NMR spectroscopy, and MS. It was found to be b-1,6-glucosaminobiose 1-phosphate acylated with (R) There is compelling evidence that the endotoxic activity of LPS is expressed by a lipid fragment of its molecule [3][4][5]. Therefore, an intensive search for potential endotoxin antagonists on the basis of lipid A is now being carried out [6].-A structure common to a number of lipid A molecules is b-1,6-D-glucosaminyl-D-glucosamine, which has a-glycosidic (1 position) and nonglycosidic (4¢ position) phosphate groups and is acylated with amide linked (at positions 2 and 2¢) and ester linked (at positions 3 and 3¢) (R)-3-hydroxy and (R)-3-acyloxy fatty acids [7]. On the other hand, according to data available so far, lipid A structural variants displaying high endotoxin antagonism have a disaccharide or monosaccharide backbone, mainly one phosphate group, and low degree of acylation [8][9][10]. Lipid A acylation patterns, which are important in binding bacteria to, and activation of, host cells [3,5] are known to depend strongly on the growth conditions [11][12][13]. We hypothesize that marine bacteria, which inhabit a specific environment (low temperature, high hydrostatic pressure, and high salinity [14]), may produce lipid A molecules of unusual structure and, possibly, of pharmacological interest.However, very little is known about the structure and function of lipid A from marine proteobacteria. Although some have been examined [15,16], only their fatty acids were identified. More recent studies have revealed some peculiarities of lipid A molecules from marine bacteria, the most pronounced being a penta-acyl-type structure [17,18].We carried out extensive structural analysis of lipid A from the Marinomonas vaga ATCC 27119 T LPS. M. vaga (formerly known as Alteromonas vaga) was first isolated from sea water off the coast of the Hawaiian archipelago in 1972 [19]. In 1983, together with Alteromonas communis, it formed a separate genus named Marinomonas [20]. M. vaga belongs to the gamma subclass of Proteobacteria. It is an aerobic, rod-shaped, polarly flagellated bacterium with psychrophilic and moderately halophilic properties. For growth, it requires Na + , Mg 2+ , and Ca 2+ in concentrations found in sea water [21]. Lipid A from this bacterium aroused our interest because it has a penta-acyl and monophosphoryl type of structure, contains short-chain (R)-3-hydroxydecanoic acid as the main acyl residue [17], and is theoretically an endotoxin antagonist.

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