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

Mice are relatively resistant to the lethal effects of endotoxin. Sensitivity to lipopolysaccharide (LPS) and monophosphoryl lipid A (MPL) can be enhanced by concurrently loading animals with D-galactosamine (D-gal). Significant diurnal variation in susceptibility to lethal toxicity was observed in D-gal loaded mice upon LPS or MPL immunostimulant challenge. In mice treated with either MPL or MPL plus D-gal, at the time of greatest toxic sensitivity, serum TNF levels were significantly higher than was seen in mice treated at a time of low sensitivity. Peritoneal exudate cells (PECs) harvested from mice treated with either D-gal or MPL displayed enhanced in vitro superoxide (SO) production. Simultaneous treatment with D-gal and MPL led to a synergistic enhancement of SO production above that induced by either xenobiotic alone. Pretreatment with the SO dismutase mimetic Cu(II) (diisopropyl salicylate)2 significantly protected mice from the lethal toxicity of D-gal-MPL challenge. PECs harvested from these same mice failed to display the elevated in vitro SO production reported above. SO elaboration in vivo, presumably by hepatocytes, PECs, and possibly other cells, subsequent to D-gal loading and LPS or MPL challenge, appears to play an important role in the lethal toxicity observed. The diurnal variation in toxicity reported in this animal model may result from TNF modulation of SO production in vivo.
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PMID:The D-galactosamine loaded mouse and its enhanced sensitivity to lipopolysaccharide and monophosphoryl lipid A: a role for superoxide. 184 21

Tumor necrosis factor alpha (TNF) is thought to play a major role in the pathogenesis of septic shock. Anti-TNF antibody was preadministered in low-dose endotoxin lethality models in which BALB/c mice were challenged with small amounts of lipopolysaccharide following their sensitization with either carrageenan (CAR) or D-galactosamine (D-GalN). Although the antibody virtually eliminated circulating TNF in both the CAR and the D-GalN models, only the D-GalN model mice were afforded survival, adding to a growing body of evidence that substances other than TNF play a key role in endotoxin-induced lethality. Further examination of sera from these mice showed a much greater elevation of interleukin-6 levels in the CAR-sensitized group than in the D-GalN-sensitized group.
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PMID:Experimental elimination of tumor necrosis factor in low-dose endotoxin models has variable effects on survival. 185 80

It is known that rodents challenged with a combination of galactosamine and endotoxin develop a fulminant hepatitis within several hours. Until now, no in-vitro correlate for this organ-specific lesion has been described. Here, in-vitro conditions have been developed which allow examination of lipopolysaccharide (endotoxin)-inducible cell injury to hepatocytes. Under these in-vitro conditions (RPMI 1640 supplemented with 10% calf serum, 40% oxygen tension) which require the presence of functionally intact Kupffer cells, a concentration-dependent lactate dehydrogenase release is inducible by different lipopolysaccharides in hepatocyte cultures from Fischer rats. It can be abrogated by polymyxin B. These co-cultures secreted tumor necrosis factor-alpha into the medium upon a lipopolysaccharide stimulus. The presence of a tumor necrosis factor-alpha antiserum reduced the major part of the endotoxin-inducible cytotoxicity. Similarities in vitro and in vivo of the cytotoxic potency of various endotoxin species and the different responsiveness of hepatocytes from two different rat strains support that this co-culture system might be useful for studying endotoxin-inducible lesions in vitro.
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PMID:Endotoxin-inducible cytotoxicity in liver cell cultures--I. 187 97

A hemagglutinin was isolated from hemocytes of the ascidian, Halocynthia roretzi, by a procedure including extraction and ion-exchange chromatography on CM-cellulose. The molecular weight of the hemagglutinin was estimated to be 120,000 by gel filtration. It was resistant to acid treatment but sensitive to alkali or heat treatment. The hemagglutinating activity was inhibited by heparin, chondroitin sulfate, and lipopolysaccharide (LPS), but not by mono- and disaccharides such as N-acetyl-galactosamine, galactose, and melibiose. The hemagglutinin showed binding ability to heparin and LPS, as demonstrated by heparin-Sepharose chromatography and centrifugation experiments, respectively. It was also found that the hemagglutinin can bind to various bacteria such as Escherichia coli, Bacillus subtilis, Vibrio anguillarum, Pseudomonas perfectomarinus, Achromobacter aquamarinus, and Alteromonas putrefaciens, and can agglutinate all of them.
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PMID:A novel lipopolysaccharide-binding hemagglutinin isolated from hemocytes of the solitary ascidian, Halocynthia roretzi: it can agglutinate bacteria. 190 30

The lipopolysaccharides of Actinobacillus actinomycetemcomitans strain Y4 and a human clinical isolate PO 1021-7 were examined by SDS/PAGE, deoxycholate/PAGE and mass spectrometry. PAGE analysis revealed an electrophoretic pattern similar to the SR-type lipopolysaccharide (LPS) of Salmonella. Deoxycholate/PAGE indicated the LPS of A. actinomycetemcomitans to consist of short sugar chains. Chemical analysis revealed the presence of thiobarbituric-acid-positive material (3-deoxy-D-manno-octulosonic acid equivalents) and four neutral sugars: glucose, galactose, D-glycero-D-manno-heptose and L-glycero-D-manno-heptose. Phosphate, glucosamine, glycine, and the fatty acids, 3-hydroxymyristic acid, myristic acid and palmitic acid, comprised the remainder of the molecule. The structure of the free lipid A revealed it to consist of a 1,6-glucosamine disaccharide esterified at C4' by a phosphomonoester. The hydroxyl group at C3 and the amide group of the non-reducing glucosamine were both acylated by 3-myristoylmyristic acid; analogous sites on the reducing glucosamine were acylated by 3-hydroxymyristic acid. Hydroxyl groups at C4 and C6' in the free lipid A were unsubstituted, with C6 being the proposed attachment site of the polysaccharide moiety. Chemical analysis revealed the presence of glycine in the intact LPS; its exact location in the A. actinomycetemcomitans LPS is still to be determined. Both intact LPS and free lipid A were highly lethal to galactosamine-sensitized mice, comparable to that of Salmonella.
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PMID:Investigation of the structure of lipid A from Actinobacillus actinomycetemcomitans strain Y4 and human clinical isolate PO 1021-7. 191 49

The antitumour antibiotic actinomycin D (Act D) and the aminosugar D-galactosamine both enhance the sensitivity of animals to bacterial lipopolysaccharide (LPS). Lipopolysaccharide stimulates macrophage membrane-bound procoagulant activity (MPCA) and tumour necrosis factor-alpha (TNF-alpha) production in vitro. We investigated the effects of LPS combined with either Act D or D-galactosamine on procoagulant and TNF-alpha production in vitro. Actinomycin D directly induced procoagulant on the malignant monocytoid cell line WEHI 265, and synergized with LPS to enhance MPCA on both WEHI 265 cells and thioglycollate-induced peritoneal exudate macrophages. In the presence of Act D, exudate macrophages expressed procoagulant in response to concentrations of LPS 100,000-fold lower than normally required. Pulsing experiments demonstrated that LPS primed these cells within 4 h to respond to Act D, whereas 4 h priming with Act D inhibited subsequent procoagulant induction by LPS. Although its effects on TNF-alpha production were less intense, low levels of Act D more than doubled TNF-alpha produced by LPS-stimulated exudate macrophages. Procoagulant expression and TNF-alpha production were not always co-ordinately expressed; interferon-gamma (IFN-gamma) synergized with LPS to enhance both responses but when IFN-gamma was combined with Act D only procoagulant was upregulated. D-galactosamine failed to affect these macrophage responses. Results indicate different in vivo mechanisms of enhancement of LPS toxicity by these two agents.
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PMID:Actinomycin D upregulates lipopolysaccharide induction of macrophage procoagulant expression and tumour necrosis factor-alpha production. 193 97

Immunochemical analysis of the capsular polysaccharide from Bacteroides fragilis NCTC 9343 revealed a novel structure composed of two distinct polysaccharides. Immunoelectrophoresis of an extract of purified surface polysaccharide from fermenter-grown organisms showed a complex precipitin profile with varying anodal mobility. DEAE-Sephacel anion-exchange chromatography of the polysaccharide extract failed to separate the majority of this aggregate. Disaggregation of this complex was accomplished by very mild acid treatment; purification was achieved by DEAE-Sephacel anion-exchange chromatography. Polysaccharide A had a neutral charge at pH 7.3, a net negative charge at pH 8.6, and an average Mr = 110,000; chemical analysis showed it to contain galactose, galactosamine, and an unidentified amino sugar. Polysaccharide B eluted from the anion-exchange column with increased salt concentration; it had a net negative charge and an average Mr = 200,000, and contained fucose, galactose, quinovosamine, galacturonic acid, and glucosamine. Neither of these polysaccharides contained detectable 3-deoxy-D-manno-octolusonic acid, and both were recognized as distinct antigens on the basis of their reactivity with monoclonal antibodies CE3 and F10, which reacted with the complex before acid treatment. These data indicate that the capsule of B. fragilis NCTC 9343 comprises two discrete, surface-exposed polysaccharides with differing physiochemical properties that are distinct from the lipopolysaccharide of this organism. The finding of two surface polysaccharides has not been described for other bacteria pathogenic to humans.
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PMID:Immunochemical characterization of two surface polysaccharides of Bacteroides fragilis. 203 68

Treatment with D-galactosamine increases sensitivity of lipopolysaccharide (LPS)-responder mice to the lethal effects of LPS, while nonresponder mice remain resistant (M.A. Freudenberg, D. Keppler, and C. Galanos, Infect. Immun. 51:891-895, 1986). In the present study it is shown that, in contrast to LPS, killed gram-negative bacteria (Salmonella abortus equi and S. typhimurium) were highly toxic for D-galactosamine-treated LPS-responder (C57BL/10 ScSN and C3H/HeN) and -nonresponder (C57BL/10 ScCR and C3H/HeJ) mice, although to a higher extent in the former strains. Also, killed gram-positive bacteria (Staphylococcus aureus, Propionibacterium acnes, and Mycobacterium phlei) exhibited toxicity for D-galactosamine-treated mice, LPS-responder and -nonresponder mice being equally susceptible. Evidently, bacterial components other than LPS may exhibit lethal effects in sensitized animals. In all cases, the lethality of LPS and of bacteria was inhibited by anti-tumor necrosis factor alpha (TNF-alpha) serum. While LPS induced TNF-alpha in vitro only in macrophages from LPS-responder mice, gram-negative and gram-positive bacteria induced TNF-alpha also in macrophages from LPS-nonresponder mice. The data show that TNF-alpha is a common endogenous mediator of the lethal activity of gram-negative and gram-positive bacteria.
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PMID:Tumor necrosis factor alpha mediates lethal activity of killed gram-negative and gram-positive bacteria in D-galactosamine-treated mice. 203 72

SDZ MRL 953, a new synthetic monosaccharidic lipid A, was investigated in vitro and in vivo for immunopharmacological activities. In experimental models of microbial infections, the compound was highly protective when it was administered prophylactically either once or three times to myelosuppressed or immunocompetent mice. The 50% effective doses of SDZ MRL 953 varied with the infectious agents and the route of its administration. In all cases, the 50% effective doses were about 10(3) times higher than those obtained with endotoxin from Salmonella abortus equi. SDZ MRL 953 was, however, less toxic than lipopolysaccharide by a factor of 10(4) to greater than 7 x 10(5) times in galactosamine-sensitized mice. The compound was also an effective inducer of tolerance to endotoxin. Hence, repeated dosing with the compound induced a transient resistance (greater than or equal to 1 week) to lethal challenges with endotoxin. In vitro, the compound was devoid of intrinsic antimicrobial activity, but it moderately induced the release of cytokines from monocytes and primed human neutrophils for the enhanced production of reactive oxygen metabolites in response to a soluble stimulus. The results presented here suggest that SDZ MRL 953 may be useful in a clinical setting for enhancing resistance to infections, particularly in patients undergoing myelosuppressive chemotherapy or irradiation, and for the prophylaxis of endotoxin shock.
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PMID:SDZ MRL 953, a novel immunostimulatory monosaccharidic lipid A analog with an improved therapeutic window in experimental sepsis. 203

Mitogenicity, lethal toxicity, induction of tumor necrotizing factor (TNF), and antitumor activity against Meth A fibrosarcoma of four chemically synthesized lipopentapeptide analogs, S-[2,3-bis(palmitoyloxy)-2R (designated as KAB-1), -2S(KAB-3)-propyl]-N-palmitoyl-(R)-cysteinyl-(S)-seryl- (S)-seryl-(S)-asparaginyl-(S)-alanine, S-[2,3-bis(palmitoyloxy)-2R(KAB-2), and -2S(KAB-4)-propyl]-N-[(2,2,2)-trichloroethoxycarbonyl]-(R)- cysteinyl-(S)-seryl-(S)-seryl-(S)-asparaginyl-(S)-alanine, of bacterial lipoprotein were investigated. These four analogs, as well as bacterial lipopolysaccharide (LPS) or synthetic Escherichia coli-type lipid A (506), were capable of increasing of [3H]thymidine into splenocytes of C3H/He mice. Although LPS and 506 did not exhibit the mitogenic activity in C3H/HeJ mice, KAB compounds showed remarkable mitogenicity. These analogs did not show the lethal toxicity at a high dose of 50 micrograms/mouse in galactosamine-loaded C57BL/6 mice. Peritoneal macrophages, stimulated with four analogs, caused the production of TNF which induces the L929 cell lysis in vitro. Twice, intravenous injections of 50 micrograms/mouse of these analogs showed weak growth inhibition of Meth A fibrosarcoma in BALB/c mice. The inhibitory effect of KAB-2 compound, which caused the strong TNF-induction among the four analogs, was the most potent. These results indicate that the biological activity of KAB-2 (R-configuration of the C-2 position in glycerol moiety with dipalmitoyl) is stronger than that of the other three analogs.
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PMID:Comparison of biologic activities of synthetic lipopentapeptide analogs of bacterial lipoprotein in mice. 206 59


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