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

The lipid A component of meningococcal lipopolysaccharide was structurally characterized by using chemical modification methods, methylation analysis, 31P nuclear magnetic resonance, and laser desorption mass spectroscopy. It was shown that Neisseria meningitidis lipid A consists of a 1,4'-bisphosphorylated beta(1'----6)-linked D-glucosamine disaccharide (lipid A backbone), both phosphate groups being largely replaced by O-phosphorylethanolamine. This disaccharide harbors two nonsubstituted hydroxyl groups at positions 4 and 6', the latter representing the attachment site of the oligosaccharide portion in lipopolysaccharide. In addition, it is substituted by up to six fatty acid residues. In the major lipid A component, representing a hexaacyl species, the hydroxyl groups at positions 3 and 3' carry (R)-3-hydroxydodecanoic acid [12:0(3-OH)], whereas the amino groups at positions 2 and 2' are substituted by (R)-3-(dodecanoyloxy)tetradecanoic acid [3-O(12:0)-14:0]. A minor portion was present as a tetraacyl lipid A component lacking either dodecanoic acid (12:0) or 12:0 and 12:0(3-OH). N. meningitidis lipid A, therefore, significantly differs from Escherichia coli lipid A by the nature and locations of fatty acids and the substitution of O-phosphorylethanolamine for the nonglycosyl (4'-P) and glycosyl phosphate.
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PMID:Structural characterization of the lipid A component of pathogenic Neisseria meningitidis. 154 29

Tumour necrosis factor alpha (TNF alpha) is a cytokine with a wide range of effects on both lymphoid and non-lymphoid cell types. By hybridization with a human TNF alpha cDNA probe the corresponding ovine cDNA was isolated from a lipopolysaccharide (LPS) stimulated alveolar macrophage cDNA library. The sequence of the cDNA clone showed that ovine TNF alpha encodes a polypeptide of 234 amino acids that, based on analysis of human TNF alpha, is processed to a protein of 157 amino acids. The nucleotide and amino acid sequences showed a high degree of homology to the equivalent human and mouse molecules. In a mammalian COS cell expression system the ovine cDNA was found to encode a protein which was able to lyse actinomycin-D treated WEHI-164 cells and induce COS cells to produce and secrete interleukin 6 (IL-6). Further experiments demonstrated the importance of sequences within the 3' untranslated region of the cDNA in determining the level of expression of ovine TNF alpha. Northern blot analysis was used to analyse the kinetics of induction of ovine TNF alpha mRNA in alveolar macrophages stimulated with a variety of mitogens. Addition of LPS increased mRNA encoding TNF alpha at 1 h and 5 h but not 24 h post stimulation. In contrast, addition of phorbol myristic acid (PMA) led to increased TNF alpha mRNA at 5 h while the combination of PMA and ionomycin increased the level of specific mRNA detected at 1 h, 5 h and 24 h. From genomic analysis ovine TNF alpha appears to exist as a single copy.
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PMID:Molecular cloning, expression and characterization of ovine TNF alpha. 178 96

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 chemical structure of Campylobacter jejuni CCUG 10936 lipid A was elucidated. The hydrophilic backbone of the lipid A was shown to consist of three (1----6)-linked bisphosphorylated hexosamine disaccharides. Neglecting the phosphorylation pattern, a D-glucosamine (2-amino-2-deoxy-D-glucose) disaccharide [beta-D-glucosaminyl-(1----6)-D-glucosamine], a hybrid disaccharide of 2,3-diamino-2,3-dideoxy-D-glucose and D-glucosamine [2,3-diamino-2,3-dideoxy-beta-D-glucopyranosyl-(1----6)-D-glucosamine], and a 2,3-diamino-2,3-dideoxy-D-glucose disaccharide were present in a molar ratio of 1:6:1.2. Although the backbones are bisphosphorylated, heterogeneity exists in the substitution of the polar head groups. Phosphorylethanolamine is alpha-glycosidically bound to the reducing sugar residue of the backbone, though C-1 is also non-stoichiometrically substituted by diphosphorylethanolamine. Position 4' of the non-reducing sugar residue carries an ester-bound phosphate group or is non-stoichiometrically substituted by diphosphorylethanolamine. By methylation analysis it was shown that position 6' is the attachment site for the polysaccharide moiety in lipopolysaccharide. These backbone species carry up to six molecules of ester- and amide-bound fatty acids. Four molecules of (R)-3-hydroxytetradecanoic acid are linked directly to the lipid A backbone (at positions 2, 3, 2', and 3'). Laser desorption mass spectrometry showed that both (R)-3-hydroxytetradecanoic acids linked to the non-reducing sugar unit carry, at their 3-hydroxyl group, either two molecules of hexadecanoic acid or one molecule of tetradecanoic and one of hexadecanoic acid. It also suggested that the (R)-3-(tetradecanoyloxy)-tetradecanoic acid was attached at position 2', whereas (R)-3-(hexadecanoyloxy)-tetradecanoic acid was attached at position 3', or at positions 2' and 3'. Therefore, the occurrence of three backbone disaccharides differing in amino sugar composition and presence of a hybrid disaccharide differentiate the lipid A of this C. jejuni strain from enterobacterial and other lipids A described previously.
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PMID:Structural analysis of the lipid A component of Campylobacter jejuni CCUG 10936 (serotype O:2) lipopolysaccharide. Description of a lipid A containing a hybrid backbone of 2-amino-2-deoxy-D-glucose and 2,3-diamino-2,3-dideoxy-D-glucose. 204 Mar 5

Tumor necrosis factor alpha (TNF-alpha) and bacterial lipopolysaccharide (LPS) induce the synthesis and cotranslational myristoylation of an 82-kDa specific protein kinase C substrate in human neutrophils. The myristic acid is covalently bound via a hydroxylamine-resistant amide linkage to the N-terminal glycine of the protein. The isoelectric point of the protein is at pH 4.6. The protein is rapidly phosphorylated when neutrophils are stimulated with chemotactic agonists or with phorbol 12-myristate 13-acetate, an activator of protein kinase C, and displays two characteristic phosphopeptides in one- and two-dimensional separation systems. Identical phosphopeptides were detected when the 82-kDa protein was phosphorylated in vitro with purified kinase C. The 82-kDa protein was immunoprecipitated by a polyclonal antiserum raised against the 87-kDa specific protein kinase C substrate from bovine brain. From these biochemical and immunological criteria it is concluded that the 82-kDa protein is the human neutrophil homolog of MARCKS, the myristoylated, alanine-rich C kinase substrate previously described in bovine and rat brain and in murine fibroblasts and macrophages. TNF-alpha and LPS prime human neutrophils for potentiated protein kinase C-dependent responses such as the respiratory burst and exocytosis. Consistent with this, these mediators do not induce the phosphorylation of MARCKS but prime the neutrophils for enhanced phosphorylation of this protein when the cells subsequently encounter activators of protein kinase C. This increase in MARCKS phosphorylation can be explained by the elevated levels of the protein observed in TNF-alpha- or LPS-treated neutrophils. Indeed, MARCKS constitutes 90% of all proteins synthesized in response to TNF-alpha or LPS. These data strongly suggest that MARCKS acts as a critical effector molecule in the transduction pathway of these important inflammatory mediators.
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PMID:Tumor necrosis factor alpha modifies agonist-dependent responses in human neutrophils by inducing the synthesis and myristoylation of a specific protein kinase C substrate. 211 1

Cellular fatty acids, phospholipid fatty acids, and lipopolysaccharide fatty acids of four strains of Helicobacter pylori were analyzed by gas-liquid chromatography. The presence of myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, 19-carbon cyclopropane fatty acid, beta-hydroxypalmitic acid, and beta-hydroxystearic acid was confirmed. In phospholipids, myristic acid and 19-carbon cyclopropane fatty acid were the major fatty acids. Hydroxy fatty acids and unsaturated fatty acids were not detected or occurred only in small amounts. The major fatty acids of lipopolysaccharides were stearic acid, beta-hydroxypalmitic acid, and beta-hydroxystearic acid. Unsaturated fatty acids and 19-carbon cyclopropane fatty acid were not found. The unusual compositions of H. pylori phospholipid and lipopolysaccharide fatty acids may have important implications for the taxonomy, physicochemical membrane properties, and biological activity of lipopolysaccharides.
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PMID:Unusual fatty acid substitution in lipids and lipopolysaccharides of Helicobacter pylori. 235 36

Human blood monocytes secrete a number of cytokines following activation including two hematopoietic growth factors, granulocyte-colony stimulating factor (G-CSF) and monocyte/macrophage-colony stimulating factor (M-CSF). The genes for these two factors can be both coordinately and independently expressed. Treatment of monocytes with phorbol myristic acid or cycloheximide induces both genes, while lipopolysaccharide selectively and transiently induces G-CSF transcripts. Interleukin-3 or granulocyte/monocyte-colony stimulating factor selectively induce M-CSF transcripts. Using nuclear run-on transcription assays and Northern blot analysis of actinomycin D-treated cells to estimate mRNA half-life, we show that the induction of both genes is due to mRNA stabilization. In resting monocytes, the levels of transcripts for both G-CSF and M-CSF are very low. Following stimulation with phorbol myristic acid, cycloheximide, lipopolysaccharide, or interleukin-3 the estimated transcription rate of both genes does not increase. However, the half-life of M-CSF mRNA increases to approximately 2 h, whereas G-CSF mRNA half-life increases to as long as 4 h. Thus, the control of CSF gene expression in monocytes is likely to involve more than one post-transcriptional mechanism.
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PMID:Regulation of granulocyte- and monocyte-colony stimulating factor mRNA levels in human blood monocytes is mediated primarily at a post-transcriptional level. 264 23

The regulation of interleukin 1 (IL 1) receptor expression on a human large granular lymphocyte cell line, YT, and fate of internalized 125I-labeled IL 1 beta (125I-IL 1 beta) were studied. YT cells were selected for this study, because this cell line expresses a large number of specific high-affinity receptor for IL 1, responds biologically to exogenously added IL 1 by expressing high-affinity IL 2 receptors, and does not produce IL 1. YT cells constitutively express approximately 7 X 10(3) IL 1 receptors/cell with a Kd approximately 10(-10) M. Neither IL 2, phorbol myristic acid, nor lipopolysaccharide affected the total binding of 125I-IL 1 beta by YT cells. In contrast, the capacity of YT cells to bind 125I-IL 1 beta when incubated at 37 degrees C for 3 to 16 hr with a low dose of purified IL 1 beta (approximately 6 U/ml) was reduced by greater than 80%. The loss of binding capability gradually recovered by 16 hr after removal of IL 1 beta from cultured YT cells. The apparent loss of IL 1 receptor expression was accompanied by the internalization of 125I-IL 1 beta into cells. Acid treatment of YT cells to remove bound 125I-IL 1 beta at 4 degrees C showed that 50% of the 125I-IL 1 beta bound to cells could no longer be recovered after 30 min at 37 degrees C, and this increased to 80% after 3 hr at 37 degrees C. Fractionation of cell extracts on Percoll gradient additionally showed 125I-IL 1 beta to appear intracellularly after receptor binding on plasma membranes, and to be successively transferred to some membranous organelles (d approximately equal to 1.037) through an intermediate density organelle (d approximately equal to 1.050), and to finally end up in lysosomal cell fractions (d approximately equal to 1.05 to 1.08) after approximately 3 hr at 37 degrees C. Only approximately 5% of internalized 125I-IL 1 beta was released into culture media by 6 hr of incubation at 37 degrees C. However, the radioactivity in the TCA soluble fraction of the culture media increased gradually by 6 hr and a lysosomotropic enzyme, ethylamine, significantly inhibited both the transfer of internalized 125I-IL 1 beta to the lysosomal fraction and the degradation of 125I-IL 1 beta. This study represents the first evidence of autoregulation of IL 1 receptors by IL 1 and internalization of IL 1 molecules after binding to receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Down-regulation of interleukin 1 (IL 1) receptor expression by IL 1 and fate of internalized 125I-labeled IL 1 beta in a human large granular lymphocyte cell line. 294 61

The present paper describes the isolation and characterization of a mutant (mutant Ts7) of Salmonella typhimurium that is conditionally defective in the incorporation of dodecanoic and tetradecanoic acid into lipopolysaccharide precursor structures. Enrichment of mutant Ts7 was achieved by free-flow electrophoresis and was based on a previous observation that at least some Salmonella mutants conditionally blocked in the synthesis of the 3-deoxy-D-manno-octulosonic acid (dOc1A)-lipid-A region exhibit higher electrophoretic mobilities than cells with intact dOc1A-lipid-A regions. Under nonpermissive conditions (42 degrees C) mutant Ts7 accumulates at least two incomplete dOc1A-lipid-A structures. One is made up of glucosamine, phosphate, dOc1A, and 3-hydroxytetradecanoic acid in a molar ratio 1.0:1.3:1.0:2.2 and is devoid of dodecanoic and tetradecanoic acid. The other structure has the same basic structure but contains hexadecanoic acid.
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PMID:Isolation of a mutant from Salmonella typhimurium producing acyl-deficient lipopolysaccharides. 306 17

To investigate the potential pathogenic mechanisms of the oral periodontopathogen Wolinella recta ATCC 33238, we have isolated its lipopolysaccharide (LPS) and determined the chemical composition and selected in vitro biological activities of the molecule. Sodium desoxycholate-polyacrylamide gel electrophoresis revealed the W. recta LPS to be an atypical smooth LPS with short O-antigenic side chains. Chemically the LPS consisted of 47.2% lipid A, 19.6% polysaccharide, 9.0% heptose, 8.5% hexosamine, 3.2% phosphate, and 0.6% 2-keto-3-deoxyoctanoate. The major fatty acids were hexadecanoic acid (25.0%), 3-OH tetradecanoic acid (23.8%), tetradecanoic acid (15.4%), 3-OH hexadecanoic acid (11.6%), and octadecenoic acid (10.9%). Rhamnose constituted 87.8% of the carbohydrates generally associated with the O antigen, with smaller amounts of glucose (5.5%), mannose (4.9%), and an unidentified sugar (1.9%). CD-1 and C3H/HeN macrophages (M phi) exposed to 1 microgram of W. recta LPS per ml released 6.0 and 10.5 ng of prostaglandin E per ml of supernatant, representing 625% and 1,306% of prostaglandin E release by the control (without LPS). Maximum prostaglandin E release occurred in CD-1 M phi exposed to 100 micrograms of LPS per ml and was equivalent to 1,542% of release by the control. Interleukin-1 (IL-1) activities in CD-1 and C3H/HeN M phi exposed to 1 micrograms of LPS per ml were 257% and 1,941% of activities in the control, respectively. Maximum IL-1 release in CD-1 M phi occurred in response to 50 micrograms of LPS per ml and represented a 927% increase over release in the control, while 100 micrograms LPS per ml stimulated maximum IL-1 release in C3H/HeN M phi that was greater than 5,000% of release by the control.
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PMID:Chemical and biological characterization of the lipopolysaccharide of the oral pathogen Wolinella recta ATCC 33238. 326 Aug 93


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