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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chemical structure of the lipid A component of lipopolysaccharides from Chromobacterium violaceum NCTC9694 was studied. Sequential treatment of lipopolysaccharide with alkali, acid, sodium borohydride and hydrazine allowed the isolation of a reduced glucosamine disaccharide. According to methylation studies and enzymic analysis with beta-N-acetylglucosaminidase the D-glucosamine residues are beta(1 leads to 6) linked. The disaccharide carries two phosphate groups, one being linked glycosidically, the other being linked as an ester to the non-reducing glucosamine. Application of a different degradation pathway shows that the ester-bound phosphate group is substituted by a 4-aminoarabinosyl residue and that the glycosidically linked phosphate group is substituted by a glucosaminyl residue. Neither the amino nor the hydroxyl groups of both these substituents are acylated. This backbone structure is shown in the following formula: (formula: see text). The amino groups of the central glucosamine disaccharide are substituted by D-3-hydroxy-dodecanoic acid, the hydroxyl groups by dodecanoic, L-2-hydroxydodecanoic and D-3-hydroxy-decanoic acid.
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PMID:The chemical structure of the lipid A component of lipopolysaccharides from Chromobacterium violaceum NCTC 9694. 86 18

The chemiluminescence of isolated neutrophils, stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine, latex, lipopolysaccharide from Escherichia coli, zymosan A, or 4 beta-phorbol 12 beta-myristate 13 alpha-acetate was inhibited up to 99% by the dose-dependent oxygen radical scavenging activity of 6 mmol/l ascorbic acid. The chemiluminescence of neutrophils in blood, stimulated with 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, or with zymosan A was inhibited 35% or 48%, respectively, by 6 mmol/l ascorbic acid. Ascorbic acid, up to 6 mmol/l, did not inhibit the release of beta-N-acetylglucosaminidase and elastase from isolated neutrophils activated by the above stimulatory agents. During neutrophil/nylon fibre interaction ascorbic acid reduced the oxygen radical production dose-dependently (77% inhibition of the chemiluminescence response at 6 mmol/l ascorbic acid), whereas the adherence was unaffected. Hypoxanthine/xanthine oxidase-generated oxygen radicals were scavenged by ascorbic acid in a dose-dependent manner (99% inhibition of the chemiluminescence response at 100 mumol/l ascorbic acid). From these results, ascorbic acid can highly be recommended for animal experiments and clinical studies in patients with trauma, shock and sepsis and for studies to prevent or reduce reperfusion injuries.
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PMID:Effect of ascorbic acid on neutrophil functions and hypoxanthine/xanthine oxidase-generated, oxygen-derived radicals. 152 46

The effect of a bacteriolytic enzyme, the endo-beta-N-acetylglucosaminidase excreted by Staphylococcus aureus (SaG) on the response of human lymphocytes to mitogens and on the immune response in mice has been studied. SaG inhibited incorporation of [3H]thymidine into TCA-precipitable material by human peripheral lymphocytes stimulated either by phytohemagglutinin or by concanavalin A, as well as formation of cytoplasmic immunoglobulin-containing cells by B lymphocytes treated with pokeweed mitogen. In all cases the level of inhibition first increased with the SaG concentrations reaching values of over 80% at an enzyme concentration of 100 micrograms/ml, and then decreased. Heat-inactivated SaG as well as SaG treated with both polyclonal and monoclonal specific antibodies or enzyme inhibitors such as chitotriose or hydrolyzed peptidoglycan had no effect on lymphocyte response to mitogens. In mice, SaG at a dose of 300 micrograms per mouse was found to cause a fourfold decrease in the anti-BSA antibody titer and an approximately 70-75% reduction in the immunoglobulin-containing cells in the spleens of mice injected with sheep red blood cells. SaG also completely abolished the enhancing effect of adjuvants such as muramyldipeptide, Freund's complete adjuvant, and Escherichia coli lipopolysaccharide. When SaG was injected into mice together with S. aureus peptidoglycan hydrolyzed either by SaG or by human lysozyme, the inhibitory effect on both production of anti-BSA circulating antibodies and appearance of Igc cells in the spleens of mice injected with sheep red blood cells was enhanced. As we know that (a) human tissues contain endo-beta-N-acetylglucosaminidases; (b) other human hexosaminidases (lysozymes) have previously been shown to interfere with the functions of immunocompetent cells; and (c) products of hexosaminidase hydrolysis of peptidoglycan (muropeptides) known to modulate immune response are ordinarily found in the urine of healthy persons, the possibility that hexosaminidases play a major role in the regulation of the immune response is raised and discussed.
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PMID:Staphylococcal endo-beta-N-acetylglucosaminidase inhibits response of human lymphocytes to mitogens and interferes with production of antibodies in mice. 190 69

Sub-microgram quantities of bacterial lipopolysaccharide (LPS) have been found to substantially reduce the intracellular catalytic activities of three representative lysosomal enzymes (namely, acid phosphatase, hexosaminidase, and beta-glucuronidase) in human monocyte-derived macrophages. This response was not associated with a concurrent increase in enzyme catalytic activity in the culture supernatant, and hence, could not be explained by mobilization of preformed material. By conducting experiments in the presence and absence of indomethacin, a cyclooxygenase inhibitor, the reduction in lysosomal enzyme catalytic activities was shown not to be dependent on the ability of LPS to induce prostaglandin E2 production. The response was not found to be the result of a more generalized LPS-dependent reduction in the ability of the cells to synthesize protein, since the presence of LPS in macrophage cultures did not appreciably affect the amount of [35S]methionine incorporated into total cellular proteins. A kinetic analysis of the effect of LPS on the down-regulation of enzyme catalytic activities indicated that this was an early response of the cells to LPS exposure. An investigation of the effects of blockade of enzyme catabolism (using the lysosomotropic weak-base, methylamine) indicated that the reduction of catalytic enzyme activities in response to LPS was probably due to a decreased rate of production of active product, rather than an enhanced rate of enzyme catabolism. This suggestion was confirmed by experiments in which the synthesis of pro-hexosaminidase (measured by biosynthetic labeling with [35S]methionine and specific immunoprecipitation of labeled pro-hexosaminidase) was found to be reduced by 42% after a 24-h exposure to LPS (although the synthesis of complement component C3 was stimulated by a factor of 4.5). It is suggested that the ability of LPS to regulate the functional expression of protein products contributes to changes in the overall functional status of these cells in response to this bacterial product.
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PMID:Bacterial lipopolysaccharide suppresses the production of catalytically active lysosomal acid hydrolases in human macrophages. 370 Apr 68

This study investigated effects of different sizes, concentrations, volumes, and surface areas of polymethylmethacrylate (PMMA) particles on human macrophages. Adherent peripheral blood monocytes isolated from five healthy individuals were exposed for 48 h to phagocytosable (0.325 micron and 5.5 microns) and nonphagocytosable (200 microns) spherical particles. Each particle size was tested over a range of concentrations (10(4)-10(11) particles per milliliter [0.325 micron], 10(2)-10(7) particles per milliliter [5.5 microns], 10(1)-10(4) particles per milliliter [200 microns]) to provide overlap in number, volume, and surface area. Primary human monocyte/macrophages were cultured in macrophage serum-free medium and 5% fetal calf serum. Macrophage viability was assessed by 3H-thymidine uptake and activation was quantified by release of interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, prostaglandin E2 (PGE2), and the lysosomal enzyme hexosaminidase. Medium alone served as a negative control; lipopolysaccharide (10 micrograms/mL) was also tested. PMMA particles were not toxic to human macrophages at any concentration tested. The smallest phagocytosable particles (0.325 micron) stimulated the release of interleukin-1 beta, interleukin-6, prostaglandin E2, and hexosaminidase at concentrations of 10(10)-10(11) particles/mL. The release of cytokines, PGE2, and hexosaminidase depended on the size, concentration, surface area, and volume of the phagocytosable particles. This study demonstrates that PMMA particle load Mi.e., the concentration of phagocytosable particles per tissue volume, characterized by size, surface area, and volume, rather than simply particle number-determines the degree of macrophage activation.
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PMID:Effect of size, concentration, surface area, and volume of polymethylmethacrylate particles on human macrophages in vitro. 884 54

We investigated the expression of the alpha- and beta-subunits of the lysosomal enzyme beta-N-acetylhexosaminidase in the BV-2 microglial cell line under different culture conditions. Beta-N-acetylhexosaminidase from BV-2 microglia cells was separated into its constituent isoenzymes on diethylaminoethyl (DEAE) cellulose, and its activity was monitored with 4-methylumbelliferyl-beta-N-acetylglucosamine and 4-methylumbelliferyl-beta-N-acetylglucosamine-6-sulphate substrates. Forms corresponding to the mouse isoenzymes A and B were present in the cells incubated in serum-supplemented medium as well as in serum-free medium. Lipopolysaccharide, a well-known activator of microglia in vitro, added to the BV-2 cells in serum-supplemented medium induced a decrease in the specific enzymatic activity determined with the 4-methylumbelliferyl-beta-N-acetylglucosamine substrate. Lipopolysaccharide had no effect on hexosaminidase isoenzyme pattern of BV-2 cells in serum-supplemented medium. The level of alpha-subunit mRNA was increased and the level of beta-subunit mRNA was decreased in BV-2 cells incubated in serum-supplemented medium plus lipopolysaccharide. In the cells incubated in a serum-free medium no significant changes in the hexosaminidase-specific activities towards the above substrates were observed. Interestingly, increased expression of alpha- and beta-subunit mRNA was evident in comparison with cultures in serum-supplemented medium. The present results suggest that the BV-2 cell line may be a useful tool to study the possible role of microglia in the metabolism of brain glycolipids.
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PMID:Constitutive expression of beta-N-acetylhexosaminidase in a microglial cell line: transcriptional modulation by lipopolysaccharide and serum factors. 937 92

Types IIA and V secretory phospholipase A2 (sPLA2) are structurally related to each other and their genes are tightly linked to the same chromosome locus. An emerging body of evidence suggests that sPLA2-IIA plays an augmentative role in long-term prostaglandin (PG) generation in cells activated by proinflammatory stimuli; however, the mechanism underlying the functional regulation of sPLA2-V remains largely unknown. Here we show that sPLA2-V is more widely expressed than sPLA2-IIA in the mouse, in which its expression is elevated by proinflammatory stimuli such as lipopolysaccharide. In contrast, proinflammatory stimuli induced sPLA2-IIA in marked preference to sPLA2-V in the rat. Cotransfection of sPLA2-V with cyclooxygenase (COX)-2, but not with COX-1, into human embryonic kidney 293 cells dramatically increased the interleukin-1-dependent PGE2 generation occurring over a 24 h of culture period. Rat mastocytoma RBL-2H3 cells overexpressing sPLA2-V exhibited increased IgE-dependent PGD2 generation and accelerated beta-hexosaminidase exocytosis. These results suggest that sPLA2-V acts as a regulator of inflammation-associated cellular responses. This possible compensation of sPLA2-V for sPLA2-IIA in many, if not all, tissues may also explain why some mouse strains with natural disruption of the sPLA2-IIA gene exhibit few abnormalities during their life-spans.
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PMID:Regulation of type V phospholipase A2 expression and function by proinflammatory stimuli. 1046 47

The A(3) adenosine receptor (A3AR) is one of four receptor subtypes for adenosine and is expressed in a broad spectrum of tissues. In order to study the function of A3AR, a mouse line carrying a mutant A(3) allele was generated. Mice homozygous for targeted disruption of the A3AR gene, A3AR(-/-), are fertile and visually and histologically indistinguishable from wild type mice. The lack of a functional receptor in the A3AR(-/-) mice was confirmed by molecular and pharmacological analyses. The absence of A3AR protein expression in the A3AR(-/-) mice was demonstrated by lack of N(6)-(4-amino-3-[(125)I]iodobenzyl)adenosine binding to bone marrow-derived mast cell membranes that were found to express high levels of A3AR in wild type mice. In A3AR(-/-) mice, the density of A(1) and A(2A) adenosine receptor subtypes was the same as in A3AR(+/+) mice as determined by radioligand binding to brain membranes. Additionally, A(2B) receptor transcript expression was not affected by ablation of the A3AR gene. A3AR(-/-) mice have basal heart rates and arterial blood pressures indistinguishable from A3AR(+/+) mice. Functionally, in contrast to wild type mice, adenosine and the A3AR-specific agonist, 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyl-carboxamide (2-Cl-IB-MECA), elicit no potentiation of antigen-dependent degranulation of bone marrow-derived mast cells from A3AR(-/-) mice as measured by hexosaminidase release. Also, the ability of 2Cl-IB-MECA to inhibit lipopolysaccharide-induced tumor necrosis factor-alpha production in vivo was decreased in A3AR(-/-) mice in comparison to A3AR(+/+) mice. The A(2A) adenosine receptor agonist, 2-p-(2-carboxyethyl)phenylamino)-5'-N-ethylcarboxamidoadenosine, produced inhibition of lipopolysaccharide-stimulated tumor necrosis factor-alpha production in both A3AR(-/-) and A3AR(+/+) mice. These results show that the inhibition in vivo can be mediated by multiple subtypes, specifically the A(3) and A(2A) adenosine receptors, and A3AR activation plays an important role in both pro- and anti-inflammatory responses.
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PMID:Disruption of the A(3) adenosine receptor gene in mice and its effect on stimulated inflammatory cells. 1066 Jun 15

The 80% aqueous acetone extract and the ethyl acetate-soluble portion from the dried fruit of Alpinia oxyphylla MIQUEL were found to show inhibitory effects on nitric oxide production in lipopolysaccharide-activated macrophages and antigen-induced degranulation in RBL-2H3 cells. A new eudesmane-type sesquiterpene, oxyphyllol A, and two eremophilane-type sesquiterpenes, oxyphyllols B and C, were isolated from the ethyl acetate-soluble portion, together with 16 known constituents. The absolute stereostructures of oxyphyllols A, B, and C were determined on the basis of chemical and physicochemical evidence. The effects of isolated components on nitric oxide production were examined, and nine constituents including oxyphyllol A and nootkatone were found to show inhibitory activity. On the other hand, five constituents inhibited the release of beta-hexosaminidase from RBL-2H3 cells.
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PMID:Absolute stereostructures of three new sesquiterpenes from the fruit of Alpinia oxyphylla with inhibitory effects on nitric oxide production and degranulation in RBL-2H3 cells. 1239 45

Three new arborinane-type triterpene glycosides, rubianosides II, III, and IV, a new arborinane-type triterpene, rubianol-g, and a new anthraquinone, rubianthraquinone, were isolated from a Chinese natural medicine, the roots of Rubia yunnanensis. The structures of the new constituents including their absolute configurations were determined on the basis of chemical and physicochemical evidence. The inhibitory effects of the isolated constituents on nitric oxide production in lipopolysaccharide-activated macrophages were examined. Among them, a cyclic peptide constituent, RA-XII and its aglycon, RA-V (deoxybouvadin), potently inhibited overproduction of nitric oxide and induction of inducible nitric oxide synthase. In addition, an anthraquinone constituent, 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone, was found to show inhibitory effects on the release of beta-hexosaminidase in RBL-2H3 cells.
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PMID:Bioactive constituents from Chinese natural medicines. XI. inhibitors on NO production and degranulation in RBL-2H3 from Rubia yunnanensis: structures of rubianosides II, III, and IV, rubianol-g, and rubianthraquinone. 1280 42


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