Lipopolysaccharide incorporation

The biomedical importance of infections by gram-negative pathogens and the consequences of septic shock have drawn much attention to lipid A, the toxic subcomponent of the lipopolysaccharide endotoxin of these organisms. A comprehensive account of the chemical structures and biological behavior of the lipid A structures is presented here by Zahrihnger, Lindner, and Rietschel. The chapter incorporates much of their own work from the... 

Lipopolysaccharide had no effect on the protein synthesis ([ HJleucine incorporation) of HC cultured alone. A number of studies concluded that this decrease in protein synthesis was not due to a single cytokine, eicosanoid, or oxygen radical (West et al., 1989). Also, the activity could not be transferred in conditioned supernatant for KC stimulated with LPS alone. However, when... 

In a similar fashion, KDO is converted to the P-linked CMP-KDO,56 56b which is incorporated into lipid A as shown in Fig. 20-10. The ADP derivative of the i -glycero-o-manno-heptose (Fig. 4-15), which is also present in the lipopolysaccharide of gramnegative bacteria, is formed from sedoheptulose 7-P in a five-step process (Eq. 20-9).57 58b... 

Daemen, T., Veninga, A., Dijkstra, J., and Scherphof, G. (1989) Differential effects of liposome-incorporation on liver macrophage activating potencies of rough lipopolysaccharide, lipid A, and muramyl dipeptide Differences in susceptibility to lysosomal enzymes. J. Immunol. 142, 2469-2474. 

The presence in bacterial lipopolysaccharides of phosphoryl-ated ethanolamine residues (1) prompted us to experiment with the incorporation of this group. When compound was treated with an activated phosphorylethanolamine derivative, prepared by the procedure shown in Figure 8, the a-phosphate [a]j) +66.7° (chloroform), was obtained in 46% yield. The reaction is similar to that with dibenzyl tributylstannyl phosphate. Thus, the new phosphorylation method may have wide application in the synthesis of C-l phosphorylated lipid A analogs. 

Blagbrough, I.S., Geall, A.J. and David, S.A. (2000) Lipopolyamines incorporating the tetraamine spermine, bound to an alkyl chain, sequester bacterial lipopolysaccharide. Bioorg. Med. Chem. Lett., 10, 1959-1962. 

Several processes in the immune response are affected by lithium in vivo and in vitro 139). The proliferative responses of hamster lymphoid cells to concanavalin A or phytohemagglutinin, which stimulate mitosis in T cells, were enhanced by lithium in a serum-free culture system. Proliferative stimulation also was obtained with lithium using the B cell mitogen lipopolysaccharide, but the B cell mitogens dextran sulfate and trypsin had no effect 140-143). Lithium increased the effects of suboptimal concentrations of stimulants, but had smaller effects on stimulation by optimal concentrations. With concanavalin A, the response to optimal stimulatory concentrations was inhibited 140). Paradoxical results such as these may be due to inhibitory effects of lithium on adenylate cyclase, or to effects on membrane transport systems 141). Most of these experiments used very high concentrations of lithium, considerably in excess of normal therapeutic doses (maximal inhibitory concentrations were 10 mM with hamster cells and 5 mM with human lymphocytes). At therapeutic levels of lithium, increased incorporation of [ H]thymidine was seen in human peripheral blood mononuclear cells. 

Fig. 3. Effect of protein L injection on the proliferation capacity of splenocytes. Transgenic 5-feature mice [46] were injected intraperitoneally with 1 mg of recombinant protein L or the control protein HEL on days 1, 3, 5, 7 and 9. Spleen cells were washed and then cultured at a concentration of 2 X 105 cells in 100 pi in 96-well, round-bottom plates for 18 h in the presence of F(ab )2 anti-human IgM or lipopolysaccharide (LPS). Incorporation of 3H-thymidine was measured and proliferation indexes were calculated. White bars = Control, non-injected mice gray bars = mice injected with HEL black bars = mice injected with protein L. 

The incorporation of Proteus mirabilis lipopolysaccharide I or Salmonella minnesota Rc lipopolysaccharide into phospholipid vesicles protected these model membranes from disruption by detergents.This suggested that the lipopolysaccharides in the outer membrane of enteric bacteria might contribute a similar protective function against the action of surfactants in the normal intestinal habitat. 

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