Influence of lipopolysaccharides and lipids A from some marine bacteria on spontaneous and Escherichia coli LPS-induced TNF-α release from peripheral human blood cells

Abstract

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.

Gram‐Negative Extremophile Lipopolysaccharides: Promising Source of Inspiration for a New Generation of Endotoxin Antagonists

“…Similarly, M. communis ATCC 27118 T lipid A (Figure g) was found to possess phosphate only on the reducing glucosamine entity and to bear five short acyl chains, three primary 10:0(3‐OH) and two secondary 10:0 (replaceable with one 12:0) and 10:0(3‐OH) . Intriguingly, Vorobeva et al demonstrated that M. communis ATCC 27118 T lipid A was unable to induce TNF‐α release from peripheral human blood cells, whereas it was capable of inhibiting TNF‐α release induced by E. coli LPS …”

Molecular Structure of Endotoxins from Gram-negative Marine Bacteria: An Update

“…As a integral part of the Outer Membrane, structural changes can occur in lipid A in response to environmental stressing conditions, mostly with regards to the fatty acids composition, to counterbalance the alterations effected by physical and chemical agents [20,21]. Lately, great attention has been paid to marine bacteria lipids A and LPSs, since they have often shown low levels of toxicity [22]. It is known that some lipid A from Gramnegative bacteria may also express antagonistic activity toward the innate immune system, competing with toxic LPSs for the active sites of the PRRs and protein mediators, thus, limiting their immunological reactivity [23].…”

Marine Compounds with Therapeutic Potential in Gram-Negative Sepsis

“…( a ) Lipid А of P. haloplanktis АТСС 14399 Т bacteria [17], where R = 3-OH-11:0, 3-OH-12:0, 3-OH-13:0, 3-OH- iso -11:0, 3-OH- iso -12:0 acid; ( b ) Lipid A of M. сommunis ATCC 27118 T [21] (I), M. vaga ATCC 27119 T [20] (II) and M. mediterranea АТСС 700492 Т [24] (III) bacteria, where (I) −R = C12:0 acid; (II) −R = С10:0, С12:0 or С12:1 acids; (III) −R = 3-ОН-С10:0 acid; С4′ atom in the molecule of this lipid A is replaced with the residue of phosphoric acid; ( c ) Lipid A C. scophthalmum CIP 104199 Т [22] and C. indoltheticum CIP 103168 Т [24]. …”

“…Due to these findings, biological properties of marine LPSs and lipid As with unusual structures (Figure 3b(I),3b(III),3c) are studied using ex vivo bioassays in human whole blood with tumor necrosis factor-α (TNF-α) as a marker of cell activation [24]. TNF-α has been shown to be the most important inflammatory cytokine that mediates multiple immunopathological features of LPS-induced sepsis [23].…”

“…As expected, the compounds effectively blocked the TNF-α-inducing activity of any toxic LPS irrespective of its source, its polysaccharide chain length, or its toxicity degree. Their inhibitory activities were dependent on the dose of the endotoxin used as the agonist: for higher doses of endotoxin, greater concentrations of lipid As were needed for efficient inhibition, thus [24] indicating a mechanism of competitive inhibition by the marine lipid As and LPSs that were tested. Interestingly, the LPS from M. communis had a much higher inhibitory activity than the well-known synthetic endotoxin antagonist E-5531, which was designed based on the lipid A from Rhodobacter capsulatus [25].…”