Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the endogenous production of a serum cytotoxic factor when recombinant interferon-gamma (rIFN-gamma) is combined with synthetic lipid A subunit analogs of low toxicity (GLA compounds). The cytotoxic activity of the serum was measured by the crystal violet staining method with L929 cells as a target. Intravenous administration of rIFN-gamma followed by intravenous administration of lipopolysaccharide induced the endogenous production of a cytotoxic factor in the serum. The priming effect of rIFN-gamma appeared immediately and persisted for approximately 20 h after the injection. Administration of lipopolysaccharide as a trigger enhanced the production of the cytotoxic factor in the serum maximally 2 h after the injection. The cytotoxic activity in the serum was completely inhibited by anti-(mouse tumor necrosis factor) (TNF) antibody. A synthetic lipid A subunit analog (GLA-60), which is much less toxic in its endotoxin activities than lipopolysaccharide or synthetic lipid A (compound 506), induced the endogenous production of serum TNF in rIFN-gamma-primed mice. GLA-60 entrapped within liposomes induced the production of serum TNF in rIFN-gamma-primed mice more effectively than GLA-60 solubilized in phosphate-buffered saline. Intravenous or intranasal administrations of rIFN-gamma followed by intranasal administration of GLA-60 produced TNF in the lung washing fluid but not in the serum, indicating that TNF production can be induced locally rather than systemically by the alteration of the administration route of the primer and trigger. These results indicate that GLA-60, a lipid A subunit analog of low toxicity, is a beneficial triggering agent in the production of endogenous TNF, as well as having other immunopharmacological properties, and may provide a basis for cancer (metastases) treatment as a result of its ability to induce endogenous TNF.
 ...
PMID:Induction of an endogenous tumor necrosis factor in mice by murine recombinant interferon-gamma combined with a lipid A subunit analog (GLA-60) of low toxicity. 249 79

We investigated the effects of the active principle of lipopolysaccharide (LPS), synthetic lipid A (compound 506), and of its related compounds GLA-60, -59 and -27, on murine macrophage activation and cytokine induction. GLA-60, which is devoid of endotoxic activity, showed interleukin-1 (IL-1)-inducing activity and activation of murine macrophages comparable to those of LPS or compound 506. The biological activities of six conjugates of GLA-60 with MDP derivatives GMD-323 to -328 were investigated in this study. All the GMD compounds except GMD-323 showed potent inducing activities for IL-1 and tumoricidal macrophages, especially GMD-324 and -326, which exhibited much higher activity than GLA-60. However, TNF- and CSF-inducing activities of these conjugates were lower than those of GLA-60. IL-1-inducing activity of the mixture of MDP derivative (GMD-267) and GLA-60 was higher than that of the conjugates (GMD-324) or that of GLA-60 and GMD-267 alone.
 ...
PMID:Adjuvant activities of synthetic lipid A subunit analogues and its conjugates with muramyl dipeptide derivatives. 267 86

A test system that allows a precise monitoring of intracellular killing of Leishmania parasites was used to measure the leishmanicidal capacity of activated macrophages from different strains of mice. Activation was obtained by exposure to dilutions of lymphokine (LK)-rich medium in the presence of ng/ml amounts of E. coli lipopolysaccharide (LPS). Highest leishmanicidal activity was displayed by macrophages from the healer mouse strain CBA/T6, whereas cells from the nonhealer strains DBA/2 and BALB/c were less effective. C3H/HeJ macrophages from a healer but LPS-unresponsive mouse strain failed to destroy leishmanias under these conditions. Experiments were then performed to determine the level of respiratory burst activity in the various macrophage populations. Hexose monophosphate shunt stimulation was higher in CBA/T6 than in BALB/c or DBA/2 macrophages, and only marginal in C3H/HeJ cells, correlating with differing leishmanicidal activities of such macrophages under the present experimental conditions. Measurements of O2- and H2O2 secretion and of chemiluminescence led to similar findings, i.e., CBA/T6 macrophages released higher amounts of oxygen metabolites than BALB/c cells activated under the same conditions, whereas C3H/HeJ cells were the least active. The results obtained by the four assays of oxidative metabolism were consistent in that endotoxin itself (in the 10 to 30 ng/ml range) stimulated the oxidative response of macrophages to a level close to that achieved by using LPS and LK together, however, only in the latter situation were parasites destroyed.
 ...
PMID:Correlation between enhanced oxidative metabolism and leishmanicidal activity in activated macrophages from healer and nonhealer mouse strains. 300 12

An analysis of the phospholipid ester-linked and the lipopolysaccharide (LPS) fatty acids and hydroxy fatty acids of six lactate-utilizing Desulfovibrio-type sulfate-reducing bacteria (SRB) has been performed using capillary gas-liquid chromatography-mass spectrometry (GLC-MS). The concentrations of normal fatty acids were essentially similar, with the possible exception of a high content of normal fatty acids in the LPS of Desulfovibrio gigas. Determination of monounsaturated acid double bond configuration was performed by GLC-MS analysis of the derivatized fatty acids. A total of nine branched chain and eight straight chain monounsaturated fatty acids was detected in the Desulfovibrio species analyzed. The major component detected in five Desulfovibrio was the 17-carbon iso-branched monoenoic acid which showed cis unsaturation [i17:1(n-7)c] seven carbons from the terminal methyl group of the fatty acid chain. D. gigas, in contrast, contained almost no unsaturated fatty acids and was greatly enriched in iso-branched 15:0. Major differences between strains were found in the phospholipid and LPS hydroxy fatty acids. These components, in addition to the i17:1(n-7)c and other characteristic branched chain unsaturated acids, can possibly be utilized as signatures of the lactate-utilizing SRB.
 ...
PMID:Extractable and lipopolysaccharide fatty acid and hydroxy acid profiles from Desulfovibrio species. 404 22

A serologically heterogeneous lipopolysaccharide (LPS) was prepared from B. fragilis IPL E323 by phenol-water extraction and purification by ultracentrifugation. The LPS was split by hydrolysis with 1 per cent acetic acid into an acid-soluble polysaccharide and insoluble material. Gel filtration of the acid-soluble material on Bio-Gel P-60 gave a high-molecular-weight fraction eluted with the void volume (Vo), which was serologically heterogeneous, and low-molecular-weight materials eluted at 2.5 x Vo and 2.7 x Vo. Some material was also eluted at 2.9-3.0 x Vo. The oligosaccharides eluted at 2.5 x Vo and 2.7 x Vo showed an antibody-neutralizing capacity similar to that of the parent LPS. Galactose, glucose and rhamnose were the only sugars present in these fractions. The material eluted at 2.9-3.0 x Vo, which contained the same neutral sugars, but at another molar ratio, was serologically inactive. SImilar results were obtained when LPS from three other B. fragilis strains were treated in the same way.
 ...
PMID:Immunochemical studies of lipopolysaccharide and partially degraded lipopolysaccharide from Bacteroides fragilis IPL E323. 618 42

A cellular (LPS I) and extracellular (LPS II) lipopolysaccharide were isolated from Moraxella glucidolytica cells grown on ethanol and from the culture fluid, respectively. Both LPS were toxic when injected to mice and chick embryos. These LPS contained glucose, galactose, glucosamine, galactosamine, 2-keto-3-deoxyoctonate and lipids. By permethylation studies, glucose was found to be linked (1 lead to 6) and (1 lead to 3) in LPS I and only (1 lead to 6) in LPS II. Galactose was the terminal non-reducing sugar. Branching occurred at positions 3 and 4 of galactose residues. LPS I was rich in alpha- and beta-hydroxylauric and alpha-hydroxymyristic acids and LPS I was detoxified by mild acid and alkaline treatments. It was also dissociated by sodium deoxycholate and chromatographed on Sephadex G-75. The main fraction was reassociated by removing the surfactant by dialysis. The morphology of LPS I and LPS II was examined by electron microscopy. LPS I (original and reassociated fractions) consisted exclusively of ribbons while LPS II contained ribbons and vesicles.
 ...
PMID:Chemical composition and ultrastructure of cellular and extracellular Moraxella glucidolytica lipopolysaccharides. 745 34

Galactose metabolism mutants of Erwinia amylovora were created by transposon insertions and characterized for their growth properties and interaction with plant tissue. The nucleotide sequence of the galE gene was determined. The gene, which encodes UDP-galactose 4-epimerase, shows homology to the galE genes of Escherichia coli, Neisseria gonorrhoeae, Rhizobium meliloti, and other gram-negative bacteria. Cloned DNA with the galE and with the galT and galK genes did not share borders, as judged by the lack of common fragments in hybridization with chromosomal DNA. These genes are thus located separately on the bacterial chromosome. In contrast to the gal operon of E. coli, the galE gene of E. amylovora is constitutively expressed, independently of the presence of galactose in the medium. The function of the galE gene but not of the galT or galK gene is required for bacterial virulence on pear fruits and seedlings. In the absence of galactose, the galE mutant was deficient in amylovoran synthesis. Subsequently, the galE mutant cells elicited host defense reactions, and they were not stained by fluorescein isothiocyanate-labelled lectin, which efficiently binds to amylovoran capsules of E. amylovora. The mutation affected the side chains of bacterial lipopolysaccharide, but an intact O antigen was not required for virulence. This was shown with another mutant, which could be complemented for virulence but not for side chain synthesis of lipopolysaccharide.
 ...
PMID:Genetics of galactose metabolism of Erwinia amylovora and its influence on polysaccharide synthesis and virulence of the fire blight pathogen. 750 2

Mild acid hydrolysis of the smooth-type lipopolysaccharide (LPS) of Pectinatus frisingensis afforded no polysaccharide but monomeric 6-deoxy-L-altrose (L-6dAlt) which was identified by anion-exchange chromatography in borate buffer, GLC/MS, 1H-NMR spectroscopy, and optical rotation. LPS was degraded with alkali under reductive conditions to give a completely O-deacylated polysaccharide, which was studied by methylation analysis, 1H-NMR and 13C-NMR spectroscopy, including sequential, selective spin-decoupling, two-dimensional correlation spectroscopy (COSY), COSY with relayed coherence transfer, two-dimensional heteronuclear 13C, 1H-COSY, one-dimensional NOE and two-dimensional rotating-frame NOE spectroscopy. It was found that the O-specific polysaccharide chain of P. frisingensis LPS is a homopolymer of 6-deoxy-L-altrofuranose built up of tetrasaccharide-repeating units having the following structure: [sequence: see text] Similarly, mild acid degradation of smooth-type LPS of Pectinatus cerevisiiphilus resulted in depolymerisation of the polysaccharide chain to give a disaccharide consisting of D-glucose and D-fucose. Study of the disaccharide by methylation analysis and alkali-degraded LPS by one-dimensional and two-dimensional 1H-NMR and 13C-NMR spectroscopy showed that the O-specific polysaccharide of P. cerevisiiphilus has the following structure: -->2)-beta-D-Fucf-(1-->2)-alpha-D-Glcp-(1-->.
 ...
PMID:Structures of the O-specific polysaccharide chains of Pectinatus cerevisiiphilus and Pectinatus frisingensis lipopolysaccharides. 755 6

Synthetic monosaccharide lipid A analogs with alkyl-branched acyl substituents instead of the usual ester-branched acyl substituents were investigated for their biological activities. The activities were compared with those of a representative synthetic monosaccharide lipid A analog with an ester branch (GLA-60) and synthetic complete lipid A (506) to estimate the role of the attaching mode of the branched side chains for expression of endotoxic activities. Among the analogs with alkyl branches, GLA-146 and GLA-147, which have C12 and C14 alkyl side chains, respectively, showed strong endotoxic activities. These analogs exhibited comparable or stronger activities than those of GLA-60 in murine macrophage activation activities to induce mediators such as tumor necrosis factors, interleukin 6, and nitric oxide and in mitogenic activity towards murine spleen cells; however, these activities were weaker than the respective activities of 506. With respect to lethal toxicity to galactosamine-sensitized mice, the analogs showed stronger activity than that of GLA-60 and activity closer to that of 506. With respect to adjuvant activity, no significant activity was observed in the analogs, while the activities of GLA-60 and 506 were strong. When lipopolysaccharide-resistant C3H/HeJ mice were used, the activities described above were not observed either for the analogs under investigation nor for GLA-60 and 506. These findings indicate that the ester type of branch in lipid A and its analogs does not play an indispensable role in the expression of various endotoxic activities. However, it may play some role in the expression of adjuvant activity and in lowering the level of toxicity.
 ...
PMID:Expression of endotoxic activities by synthetic monosaccharide lipid A analogs with alkyl-branched acyl substituents. 789 Apr 8

Lipid A is the active principle of lipopolysaccharide (LPS). Synthetic lipid A analogues with monosaccharide backbones, GLA-60, GLA-69 and GLA-58, which exhibit potent, weak and scarce agonistic activities of LPS, respectively, induced tolerance against LPS lethality in galactosamine-(GalN)-sensitized mice while none of them were pyrogenic in rabbits. The tolerance-inducing mechanisms were investigated focusing on the regulation of tumor-necrosis-factor-alpha(TNF-alpha)-mediated lethal pathway of LPS. Induction of serum TNF-alpha in LPS-challenged mice was suppressed by prior administration of these analogues as well as LPS. Prior treatment of murine macrophages with the substances suppressed LPS-stimulated TNF-alpha production in the culture supernatant and TNF-alpha mRNA expression in the cells as well. Lethal toxicity of TNF-alpha in GalN-sensitized mice was effectively suppressed by prior treatment with LPS, GLA-60 and GLA-69 but not by GLA-58. This protective effect was suggested to be mediated by endogenous TNF-alpha, which was induced by prior treatment with the effective substances, because either neutralization of endogenously induced TNF-alpha activity with an antibody or deletion of its induction by using LPS-resistant C3H/HeJ mice reduced the protective effect, and a detectable amount of TNF-alpha was produced by stimulating macrophages with the effective substances but not with GLA-58. These results indicated that multiple regulation steps (one is prior to and the others are following TNF-alpha production) are participating in the tolerance induction by LPS and some lipid A analogues and that GLA-58 is a characteristic compound which induces the tolerance by only blocking the step prior to TNF-alpha production.
 ...
PMID:Multistep regulation mechanisms for tolerance induction to lipopolysaccharide lethality in the tumor-necrosis-factor-alpha-mediated pathway. Application of non-toxic monosaccharide lipid A analogues for elucidation of mechanisms. 816 21


<< Previous 1 2 3 4 5 6 Next >>