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)

A 10-50-fold, biphasic increase in the rate of 32Pi labeling of eIF-4E was closely correlated with the induction of protein and glycoprotein biosynthesis when resting murine splenic B lymphocytes (B cells) were activated by bacterial lipopolysaccharide or the combination of phorbol 12-myristate 13-acetate and ionomycin. The fraction of eIF-4E which was phosphorylated only increased from 46% in resting cells to 83% in lipopolysaccharide-activated cells. This discrepancy between the increase in the fraction of phosphorylated eIF-4E and the increase in 32Pi labeling suggested that the phosphoryl group of eIF-4E turns over slowly in resting B cells compared with activated cells. The turnover rate for the eIF-4E phosphate moiety in lipopolysaccharide-activated cells was rapid (t1/2 = 2 h) in comparison to the eIF-4E polypeptide chain, which did not turn over detectably in 6 h. Neither protein kinase C nor a cyclic nucleotide-dependent protein kinase appeared to be involved in eIF-4E phosphorylation in B cells, based on the observations that the metabolic labeling of eIF-4E by 32Pi was insensitive to the protein kinase inhibitors H-7 and HA1004, and that maximal labeling occurred after protein kinase C activity was "down-regulated" to very low levels in phorbol 12-myristate 13-acetate/ionomycin-activated cells. Dephosphorylation in vivo was blocked by okadaic acid (IC50 = 200 nM). These results indicate that a rapid phosphorylation-dephosphorylation of eIF-4E is associated with high translation rates during the activation of B cells, and implicate protein phosphatase-1 (or possibly-2A) in the dephosphorylation of the initiation factor.
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PMID:Increased rate of phosphorylation-dephosphorylation of the translational initiation factor eIF-4E correlates with the induction of protein and glycoprotein biosynthesis in activated B lymphocytes. 224 37

Five cesarean-derived, colostrum-deprived pigs were given three adjuvant-supplemented subcutaneous and one intravenous injection of the purified 104-kDa hemolysin from serotype 1 Actinobacillus pleuropneumoniae CM-5. Six control animals received phosphate-buffered saline only. Five of six control pigs died within 24 h after challenge. The sixth control pig was moribund and euthanized after 48 h. All six pigs had pleuropneumonia, and A. pleuropneumoniae was isolated from all six lungs. None of the vaccinated pigs died as a result of challenge. After being euthanized, two pigs in this group had no lung lesions but three had chronic pleuropneumonia involving 10, 20, and 40% of the lung tissue. A. pleuropneumoniae was isolated from lung lesions of these three animals but not from the two pigs without lesions. The prechallenge hemolysin-neutralizing antibody titers in the vaccinated pigs were 1:10,900, 1:10,600, 1:4,800, 1:3,900, and 1:3,000, in order of increasing lung involvement. None of the control pigs had neutralizing antibodies. Enzyme-linked immunosorbent assay (ELISA) antibodies to capsule, lipopolysaccharide, and hemolysin were not detected in serum samples collected from the control pigs. In the vaccinated group, prechallenge sera did not contain ELISA antibodies to capsule or lipopolysaccharide. ELISA antibodies to the hemolysin were detected only in the prechallenge and postchallenge serum samples. These results indicate that pigs immunized with the 104-kDa hemolysin of serotype 1 A. pleuropneumoniae are protected against challenge with virulent bacteria. The association between neutralizing antibodies and protection indicates indirectly that the hemolysin is an important virulence factor.
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PMID:Humoral antibody response and protective immunity in swine following immunization with the 104-kilodalton hemolysin of Actinobacillus pleuropneumoniae. 225 12

The ability of synthetic lipid A analogs to induce prostaglandin synthesis in macrophages was compared with that of native lipopolysaccharide. The synthetic preparations comprised monomeric or dimeric derivatives of D-glucosamine with different patterns of substitution by phosphate and tetradecanoic, (R)-3-hydroxytetradecanoic, and (R)-3-tetradecanoyloxytetradecanoic acid. All of these preparations are structurally distinct from native lipid A (principally regarding the position of fatty acid substitution) and hence have been previously shown to be endotoxically inactive in many biological tests. It was found that many of these synthetic samples exhibit strong activity in inducing prostaglandin E2 and prostaglandin F2 alpha, with some of them having activity comparable to that of lipopolysaccharide. Experiments with macrophages of C3H/HeJ mice enabled us to differentiate between endotoxin-specific (in the case of dimeric preparations) and endotoxin-nonspecific (for monomeric preparations) mechanisms for the induction of prostaglandins. These results indicate that there is a difference in the mechanism of induction of prostaglandin synthesis between monomeric lipid A's and dimeric or native lipid A structures.
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PMID:Endotoxic induction of prostaglandin release from macrophages by nontoxic lipid A analogs synthesized chemically. 229 51

The synthesis of periplasmic beta(1-2)glucan is required for crown gall tumor formation by Agrobacterium tumefaciens and for effective nodulation of alfalfa by Rhizobium meliloti. The exoC (pscA) gene is required for this synthesis by both bacteria as well as for the synthesis of capsular polysaccharide and normal lipopolysaccharide. We tested the possibility that the pleiotropic ExoC phenotype is due to a defect in the synthesis of an intermediate common to several polysaccharide biosynthetic pathways. Cytoplasmic extracts from wild-type A. tumefaciens and from exoC mutants of A. tumefaciens containing a cloned wild-type exoC gene synthesized in vitro UDP-glucose from glucose, glucose 1-phosphate, and glucose 6-phosphate. Extracts from exoC mutants synthesized UDP-glucose from glucose 1-phosphate but not from glucose or glucose 6-phosphate. Membranes from exoC mutant cells synthesized beta(1-2)glucan in vitro when exogenous UDP-glucose was added and contained the 235-kilodalton protein, which has been shown to carry out this synthesis in wild-type cells. We conclude that the inability of exoC mutants to synthesize beta(1-2)glucan is due to a deficiency in the activity of the enzyme phosphoglucomutase (EC 2.7.5.1), which in wild-type bacteria converts glucose 6-phosphate to glucose 1-phosphate, an intermediate in the synthesis of UDP-glucose. This interpretation can account for all of the deficiencies in polysaccharide synthesis which have been observed in these mutants.
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PMID:Biochemical characterization of avirulent exoC mutants of Agrobacterium tumefaciens. 230 61

Antitumor activity, mitogenicity, and lethal toxicity of chemically synthesized lipid A analogs, acylglucosamine-4- or -6-phosphate with the alpha, beta-hydroxyacyl, acyloxyacyl, or hydroxyacyloxacyl groups at the C-2 and C-3 positions, were examined. Meth A fibrosarcoma cells (5 X 10(5)) were inoculated subcutaneously into BALB/c mice on day 0, and six compounds (50 micrograms/mouse) were administered intravenously on days 7 and 9. Although the antitumor activity of these compounds was weaker than that of natural lipopolysaccharide (LPS) or the synthetic lipid A analog (506) of Escherichia sp type, all groups exhibited tumor inhibition rates of 40% to 50% and delayed tumor growth. Six compounds, with the exception of compound A-173 (with the hydroxytetranoyl group at the C-2 and C-3 positions), were capable of increasing the incorporation of [3H]thymidine into cultured splenocytes of C57BL/6 mice, and caused lethal toxicity in C57BL/6 mice sensitized with galactosamine. However, these compounds had lower toxicity than bacterial LPS (about 500- to 1,000-fold). Compounds A-172 and A-174, which have the same structure except for the C-4 or C-6 position of the phosphate group, exerted similar antitumor activity, mitogenicity, and lethality. The results discussed above indicate that the biologic activity of these compounds correlates with the carbon number of fatty acid but is not affected by the different location of the phosphate group. Furthermore, it seems that the difference between the alpha, beta-hydroxy position of fatty acid and the R or S configuration does not alter the biologic effects.
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PMID:Antitumor activity against Meth A fibrosarcoma and biologic activities of synthetic monosaccharide analogs of lipid A in mice. 236 54

The interaction of lipopolysaccharide-binding sites of mouse macrophages with the Lipid A region of endotoxins (LPS) was demonstrated by direct binding of labeled Lipid A conjugates, by inhibition of the binding of labeled LPS with anti-Lipid A monoclonal antibodies, and by the considerable reduction of this binding after chemical and enzymatic removal of the fatty acid esters of the LPS. The substructures of Lipid A required for the specific binding of LPS to macrophages were analyzed by the use of synthetic lipids consisting of mono- or disaccharide derivatives of glucosamine. The two phosphate groups of Lipid A (at positions 1 and 4') as well as certain hydroxyl groups, appeared to play a critical role in the binding. However, the reactivities of the synthetic lipids with the macrophage surface, as compared with those with anti-Lipid A antibodies, could hardly be explained by the existence of a single LPS receptor, and suggested the presence, on the macrophage surface, of different LPS-binding sites that recognize different substructures or spatial configurations of the lipid moiety of endotoxins.
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PMID:Specific binding of lipopolysaccharides to mouse macrophages--II. Involvement of distinct lipid a substructures. 240 45

Five anti-core glycolipid monoclonal antibodies (MAb) (four against Escherichia coli J5 lipopolysaccharide [LPS] and one against the Re core glycolipid of Salmonella typhimurium) were characterized using LPS from several rough and smooth strains and derivatives of E. coli J5 LPS, obtained by N acetylation and hydrolysis. The MAb against E. coli J5 were not only weakly cross-reactive with clinical isolates, whereas the anti-Re MAb was highly cross-reactive. The MAb differed in their reaction pattern with E. coli J5 LPS. MAb 4-7B5 (immunoglobulin M) and MAb 4-6A1 (immunoglobulin G1) cross-reacted with LPS of Salmonella minnesota R5 and S. typhimurium Ra and Rc and little with Re and lipid A. The dominant binding site of these MAb was located in the glucose-heptose-heptose region and was independent of phosphate substitution. The MAb 4-9A1 reacted with the terminal part of the core region (glucose-heptose) and was dependent on phosphate substitution of the LPS. The MAb BA7 (immunoglobulin G3) was E. coli J5 LPS specific and reacted with the glucosaminyl-heptose disaccharide. Antibody 8-2C1 was directed against the common parts of LPS, 3-deoxy-D-manno-octulosonic acid, and lipid A, which are not (or only weakly) recognized by the four anti-J5 LPS MAb. Thus, MAb that are not cross-reactive can be directed against at least three different antigenic determinants present on the core oligosaccharide of E. coli J5 LPS.
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PMID:Characterization of anti-core glycolipid monoclonal antibodies with chemically defined lipopolysaccharides. 240 71

The endotoxic activity of lipopolysaccharide (LPS) extracted from the envelope of Bacteroides fragilis is low compared with that of LPS from Escherichia coli, Salmonella, and other Enterobacteriaceae. Thus, pyrogenicity, the ability to prepare for or provoke the local Shwartzman reaction, and the ability to induce the production of interleukin 1 are reduced by 100- to 1,000-fold. Structural analyses of characterized B. fragilis LPS have shown that its lipid A is composed of a beta 1,6-linked D-glucosamine disaccharide that has the following properties: (1) a phosphate group on C1 of the reducing amino sugar, (2) amide- and ester-linked 3-hydroxylated branched and nonbranched long-chain (C15-C17) fatty acids, (3) an average of five fatty acids per glucosamine disaccharide, and (4) the core and O-antigenic saccharide chain linked to C6 of the nonreducing glucosamine residue. Although structurally similar to lipid A of E. coli, the lipid A of B. fragilis differs by its lack of the phosphate group on C4 of the nonreducing amino sugar and by the presence of fewer and different fatty acids. These differences explain the low endotoxic activity of B. fragilis LPS. The core and O-antigenic chain are linked to lipid A via a phosphorylated 2-keto-3-deoxyoctonate (KDO) residue. The saccharide chain is short and is composed of L-rhamnose, D-glucose, and D-galactose, with the O-antigenic specificity determined by a beta 1,6-linked D-galactose oligomer. This O-antigenic specificity was present in 14 of 17 strains of B. fragilis that were investigated.
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PMID:Structure-activity relationships in lipopolysaccharides of Bacteroides fragilis. 240 67

The major outer membrane proteins of Haemophilus influenzae type b (Hib), designated P5 and P6 (R.S. Munson, Jr., J.L. Shenep, S.J. Barenkamp, and D.M. Granoff, J. Clin. Invest. 72:677-684, 1983), were purified to homogeneity and partially characterized. P5 was insoluble in octylglucoside-NaCl and could be extracted with 1% sodium dodecyl sulfate (SDS) in 20 mM phosphate (pH 7.5). Solubilized P5 was further purified on hydroxylapatite in 0.1% SDS. The purified protein had an apparent molecular weight of 27,000 as determined by SDS-polyacrylamide gel electrophoresis after sample preparation at room temperature. The protein migrated with an apparent molecular weight of 35,000 after heating for 30 min at 100 degrees C in the presence of 10% beta-mercaptoethanol (beta ME). Rabbit antisera prepared against the purified preparation immunoprecipitated solubilized protein P5 but had no protective activity in the infant rat bacteremic model. The SDS-insoluble residue was further extracted with 1% SDS-0.5 M NaCl-0.1% beta ME at 37 degrees C. A single outer membrane protein, designated P6, with an apparent molecular weight of 16,000, remained insoluble under these conditions. Antiserum prepared against this insoluble fraction contained antibodies which, after removal of anti-lipopolysaccharide antibody, immunoprecipitated P6 and protected infant rats challenged with Hib. Protein P6 could be released from the insoluble cell wall in the presence of SDS-NaCl-beta ME at 60 degrees C. Thus, proteins P5 and P6 could be purified from the cell envelope of Hib. Based on the results from infant rat passive protection experiments, antigens in the P6-cell wall fraction merit further investigation as possible vaccine components. In contrast, epitopes on protein P5 did not appear to elicit protective antibody.
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PMID:Purification and partial characterization of outer membrane proteins P5 and P6 from Haemophilus influenzae type b. 241 57

We established hybridoma cell lines producing monoclonal antibodies against enterobacterial common antigen (ECA) and a substructure of the outer core of different Escherichia coli lipopolysaccharides (LPSs). Anti-ECA antibodies 865 and 898 reacted with ECA in extracts of heated E. coli and with ECA-bound R1 and R4 core-containing LPS preparations, as well as with a purified sample of ECA from Salmonella montevideo. Antibody 865, but not antibody 898, cross-reacted with K5 capsular polysaccharide, suggesting that 4-linked alpha-N-acetylglucosamine is part of an antigenic determinant shared by both K5 polysaccharide and ECA. Anti-LPS antibody 786 recognized an outer core structure common to E. coli K-12, B, R2, and R4 core type LPS, but not to R1 and R3 core type LPS. Its most probable target is the trisaccharide sequence Hexp(1----2)-alpha-D -Glcp(1----3) alpha-D-Glcp----(Hepp) (where Hex is hexose, p is phosphate, Glc is glucose, and Hep is heptose), the first glucose being the immunodominant moiety. These monoclonal antibodies may be used not only for the detection of ECA, K5, and LPS core structures but also for analysis of the molecular forms resolved on polyacrylamide gels (banding patterns) of both ECA and LPS, independently of one another.
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PMID:Monoclonal antibodies to enterobacterial common antigen and to Escherichia coli lipopolysaccharide outer core: demonstration of an antigenic determinant shared by enterobacterial common antigen and E. coli K5 capsular polysaccharide. 241 23


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