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

Endotoxin was shown to depress neutrophil bactericidal activity while enhancing Nitro Blue Tetrazolium reduction and hexose monophosphate shunt activity. Separation of bactericidal action from oxidative metabolism suggests that the effect of endotoxin might involve the formation of reactive oxygen radicals such as superoxide. Chemiluminescence often accompanies metabolic activation of polymorphonuclear neutrophils (PMNs). However, human PMNs did not show chemiluminescence when challenged with endotoxin (lipopolysaccharide; LPS) or lipid A. Superoxide formation was also unaffected by endotoxin. In contrast, preincubation of PMNs with LPS for 30 min produced significant depression of chemiluminescence, oxygen consumption, and superoxide formation. Decreased chemiluminescence was not the result of complement consumption. In a cell-free system, superoxide was not scavenged by LPS, nor did LPS stimulate superoxide dismutase. Oxidase enzymes for reduced nicotinamide adenine dinucleotide or reduced nicotinamide adenine dinucleotide phosphate harvested from broken cells were not affected by LPS. The toxicity of LPS may reside in its ability to activate the PMNs while simultaneously blocking bactericidal capacity.
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PMID:Endotoxin in vitro interactions with human neutrophils: depression of chemiluminescence, oxygen consumption, superoxide production, and killing. 22 88

Normal mouse embryo fibroblasts (MEF) are killed by treatment with low doses of interferon gamma (IFN-gamma) in combination with lipopolysaccharide (LPS). This cytotoxicity has previously been shown to represent an active suicidal reaction. Here we show that the time period between first contact with IFN-gamma/LPS (t = 0 h) and cell death (t = 48 h) can be separated into two distinct periods, during which glycolytic metabolism of glucose either has a positive (8-24 h) or a negative (30-48 h) effect on cytotoxicity. During the first period (8-24 h), withdrawal of glucose from the culture medium, or inclusion in the medium of the glycolytic inhibitors deoxy-D-glucose, NaF or iodoacetate, prevented later cell death. During the second period (30-48 h), withdrawal of glucose or supplementation of the culture medium with glycolytic inhibitors was no longer protective; instead it was a requirement for cell suicide to occur. Glycolytic activity during the first period was found to be increased twofold in LPS-treated MEF and almost threefold in IFN-gamma/LPS-treated MEF. A variety of agents were found both to protect cells against IFN-gamma/LPS-induced cytotoxicity and to inhibit increased glycolysis in these cells: glucocorticoids, the serine-type protease inhibitor N-acetyl-DL-phenylalanine-beta-naphthyl ester, the ADP-ribosylation inhibitors 3-aminobenzamide and nicotinamide, and the transcription and translation inhibitors actinomycin and cycloheximide. Mitochondrial function, although normal in LPS-treated cells, was markedly depressed in IFN-gamma/LPS-treated MEF. Specifically, malate- and succinate-driven respiration was found to be impaired. Furthermore, IFN-gamma/LPS-treated MEF contained one-third of the ATP level of LPS-treated MEF. Withdrawal of L-arginine from the culture medium prevented cell death in IFN-gamma/LPS-treated MEF. N-Methyl-L-arginine, which is an inhibitor of nitric oxide (NO.) biosynthesis from L-arginine, also inhibited cell death. In conclusion, we propose that cell death in our experiments is due to an L-arginine/glycolysis-dependent impairment of mitochondrial respiration.
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PMID:Interferon-gamma/lipopolysaccharide-treated mouse embryonic fibroblasts are killed by a glycolysis/L-arginine-dependent process accompanied by depression of mitochondrial respiration. 193 71

Early changes in hepatic carbohydrate metabolism without apparent hepatocyte dysfunction were reported previously in mice infected with Listeria monocytogenes. This study was undertaken to examine possible imbalance in host regulatory mechanisms which might be responsible for these changes. Female CD-1 mice fasted 12 hr prior to the experiments were injected intraperitoneally with 10(5), 10(6), or 10(7)Listeria. Control mice received either 10(9) heat-killed Listeria or 150 mug of Salmonella typhimurium lipopolysaccharide. Hepatic glycogen, adenosine triphosphate (ATP), adenosine diphosphate (ADP), and nicotinamide adenine dinucleotide (NAD) (NAD(+), NADH, NADP(+), and NADPH) levels were assayed periodically. Activities of ATP hydrolyzing enzyme and NAD glycohydrolase were measured at various intervals after infection. Decreases in glycogen occurred as early as 10 hr after infection. Responses in the controls differed from those in infected mice. Hepatic ATP levels decreased as early as 10 hr after infection, with concomitant increases noted in ADP. Hepatic ATP hydrolyzing enzyme activity increased as the infection progressed. Decreases were noted in hepatic NAD levels, with the greatest reduction in the reduced form of NAD. Slight changes were observed after 10 hr, and greater differences were noted 20 hr after infection. The magnitude of these biochemical changes appeared to be dose-dependent. Significant increases in hepatic NAD glycohydrolase activity were noted as the infection progressed. Small but significant increases in serum inorganic phosphate were noted 10 and 20 hr after infection, with a larger increase observed 30 hr after infection. The results indicate impairment of host energy metabolism early in the course of experimental listeriosis.
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PMID:Mechanisms of pathogenesis in Listeria monocytogenes infection. V. Early imbalance in host energy metabolism during experimental listeriosis. 434 93

Escherichia coli O127:B8 lipopolysaccharide (LPS) inhibited oxygen consumption by isolated mouse liver mitochondria at 10 micrograms of LPS per mg of protein when glutamate + malate was the substrate and adenosine 5'-diphosphate had been added (state 3 respiration), but had little effect when adenosine 5'-diphosphate was not added (state 4 respiration). LPS stimulated state 4 respiration at 10 micrograms/mg of mitochondrial protein when succinate was the substrate but had little effect on state 3 respiration. Lipid A from Shigella sonnei at 2 micrograms/mg of mitochondrial protein also stimulated state 4 respiration but did not affect state 3 respiration with succinate as the substrate. Lipid A, unlike LPS, caused a decrease in the adenosine 5'-diphosphate/O ratio. LPS at 100 micrograms/mg of mitochondrial protein impaired the reduction of cytochromes aa3, c, and b when succinate was the substrate but not when reduced nicotinamide dinucleotide, dithionite, or glutamate was the substrate.
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PMID:Action of bacterial lipopolysaccharide on the respiration of mouse liver mitochondria. 698 63

Isolated membranes of the cell wall-less stable protoplast L-form of Proteus mirabilis were characterized by density gradient centrifugation and by assay for their major chemical constituents, proteins, phospholipids and lipopolysacchartide, and for some specific marker enzymes of the cytoplasmic membrane. In most of the analyzed properties the L-form protoplast membrane resembled the bacterial cytoplasmic membrane, with some notable modifications. Considerable amounts of lipopolysaccharide, normally an exclusive constituent of the outer membrane, were found. Furthermore, the L-form membranes contained the functions of the reduced nicotinamide adenine dinucleotide oxidase system, of D-lactate dehydrogenase (EC 1.1.1.28) and of succinate dehydrogenase (EC 1.3.99.1) at specific activities comparable to, or in some cases considerably higher than, those present in cytoplasmic membranes of the bacterial form. Of two peptidoglycan DD-carboxypeptidase/transpeptidases (EC 3.4.17.8 and EC 2.3.2.10). which are normally present in the cytoplasmic membrane of the bacterial form of P. mirabilis, the membrane of the protoplast L-form contained only one. Electron microscopy of thin sectioned L-form protoplasts showed extensive heterogeneity of membraneous structures. In addition to the single membraneous integument, internal membrane-bounded vesicles and multiple stacks of membranes were present, as the result of unbalanced growth and membrane synthesis in the L-form state.
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PMID:Membranes of the protoplast L-form of Proteus mirabilis. 700 76

In Salmonella minnesota lipopolysaccharide the lipid A backbone, a substituted diphosphorylated beta 1,6-linked D-glucosamine disaccharide molecule, carries approximately seven residues of fatty acids: one each of dodecanoic, hexadecanoic, D-3-hydroxytetradecanoic and D-3-O-(tetradecanoyl)-tetradecanoic acid in ester linkage and two of D-3-hydroxytetradecanoic acid in amide linkage. In the present study it is shown that treatment of the lipopolysaccharide with alkali at elevated temperature leads, through a beta-elimination reaction, to the generation of amide-bound delta 2-tetradecanoic acid. This suggested that the 3-hydroxyl group of amide-bound hydroxy fatty acids carried a substituent. To elucidate the nature of the substituent, free Salmonella lipid A was methylated with methyl iodine in the presence of silver salts followed by mild acid hydrolysis, a procedure which is known to cleave amide (and not ester) bonds selectively. In the hydrolysate, by means of combined gas-liquid chromatography/mass spectrometry the methyl esters of 3-O-(dodecanoyl)-tetradecanoic and 3-O-(hexadecanoyl)-tetradecanoic acid were identified. This shows that in lipid A amide-linked 3-hydroxytetradecanoic acid residues are 3-O-acylated by dodecanoic and hexadecanoic acid, respectively. Quantitative analyses suggest that the Salmonella lipid A backbone is substituted by four D-3-hydroxytetradecanoyl residues, two being present as esters and two as amides. The nonhydroxylated fatty acids are not bound directly to the backbone. Rather, they are attached to hydroxyl groups of 3-hydroxytetradecanoyl residues: specifically, tetradecanoic acid substitutes ester-bound and dodecanoic and hexadecanoic acid amide-bound 3-hydroxytetradecanoic acid.
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PMID:The chemical structure of lipid A. Demonstration of amide-linked 3-acyloxyacyl residues in Salmonella minnesota Re lipopolysaccharide. 708 25

Nitric oxide (NO) is a potent mediator involved in many biological functions including inflammation and non-specific immunity. Murine macrophages possess the prototype of high-output NO synthase which is not constitutively expressed but induced within a few hours by immunological stimuli. In this study, we explored the possibility of controlling the activity of the inducible NO synthase by interfering with the transduction signal which triggers its induction, in the RAW 264.7 macrophage cell line. We found that nicotinamide, an inhibitor of ADP-ribosylation, prevented NO synthase induction in RAW 264.7 cells after stimulation with interferon gamma (IFN-gamma) and lipopolysaccharide (LPS). Furthermore, the level of NO synthase mRNA was measured by Northern-blot analysis and we found that nicotinamide prevents expression of NO synthase mRNA in IFN-gamma- and LPS-stimulated cells. Nicotinamide was also found to inhibit other macrophage functions expressed in response to IFN-gamma, i.e. tumour necrosis factor secretion and the expression of the Ia antigen of the major histocompatibility complex. Analysis of the pattern of ADP-ribosylated proteins revealed that nicotinamide as well as cholera toxin prevented the ADP-ribosylation of a 107-117 kDa protein found constitutively ADP-ribosylated in stimulated and non-stimulated macrophage extracts. Together, our results indicate ADP-ribosylation as a crucial point of the signalling pathway which leads to NO synthase mRNA induction.
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PMID:Nicotinamide inhibits nitric oxide synthase mRNA induction in activated macrophages. 750 33

The effect of staphylococcal enterotoxin B (SEB)-elicited inducible nitric oxide synthase (iNOS) in mouse endothelial cells was investigated. Results showed that SEB stimulated the same level of NO production in gamma interferon (IFN-gamma)-primed cells as did trichloroacetic acid-extracted lipopolysaccharide. The kinetics of induced NO production and expression of mRNA for iNOS differed markedly in endothelial and macrophage cells. Induced endothelial nitrite production was transient and was 15 to 20% of that generated by macrophage cells; mRNA levels peaked by 2 h and then steadily declined, whereas macrophage message levels continually increased. The ability of endothelial cells to produce SEB-induced NO depended on priming with IFN-gamma, although detectable mRNA could be elicited by SEB alone. Induction of endothelial iNOS mRNA was inhibited by cycloheximide, which indicated a requirement for de novo protein synthesis. Niacinamide and interleukin-10 significantly reduced SEB-induced endothelial NO production. Both are reported to affect IFN-gamma-induced class II major histocompatibility complex (MHC) expression on antigen-presenting cells. Niacinamide reduced iNOS mRNA levels and markedly reduced IFN-gamma induction of endothelial class II MHC surface antigen. Interleukin-10 did not consistently reduce iNOS mRNA expression and had no effect on IFN-gamma induction of endothelial class II MHC surface antigen. These results suggest that SEB interacts with IFN-gamma-primed endothelial cells to elicit induced NO and that this induction can be effectively modulated at the receptor or transcriptional level.
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PMID:Regulation of staphylococcal enterotoxin B-elicited nitric oxide production by endothelial cells. 752 48

1. In RAW 264.7 macrophages, lipopolysaccharide (LPS) and gamma-interferon (IFN gamma) alone or in combination stimulated the induction of nitric oxide synthase (iNOS) activity and increased the expression of the 130 kDa isoform of NOS. 2. LPS-induced NOS activity was reduced by incubation with CD14 neutralising antibodies and abolished in macrophages deprived of serum. 3. LPS stimulated a small increase in protein kinase C (PKC) activity in RAW 264.7 macrophages which was dependent on the presence of serum. However, IFN gamma did not potentiate LPS-stimulated PKC activity. 4. The protein kinase C inhibitor, Ro-318220, abolished both LPS- and IFN gamma-stimulated protein kinase C activity and the induction of NOS activity. 5. LPS- and IFN gamma-induced NOS activity was reduced by the tyrosine kinase inhibitor genestein. Genestein also reduced LPS-stimulated protein kinase C activity but did not affect the response to the protein kinase C activator, tetradecanoylphorbol acetate (TPA). 6. Nicotinamide, an inhibitor of poly-ADP ribosylation, abolished LPS- and IFN gamma-induced NOS activity. 7. Brefeldin A, an inhibitor of a factor which stimulates nucleotide exchange activity on the 21 kDa ADP-ribosylation factor, ARF, reduced LPS- and IFN gamma-induced NOS activity by approximately 80%. 8. These results suggest the involvement of protein kinase C, tyrosine kinase and poly-ADP ribosylation pathways in the regulation of the induction of nitric oxide synthase in RAW 264.7 macrophages by LPS and IFN gamma.
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PMID:Protein kinase C and tyrosine kinase pathways regulate lipopolysaccharide-induced nitric oxide synthase activity in RAW 264.7 murine macrophages. 753 21

A number of cell types possess an L-arginine-nitric oxide (NO) pathway. We studied the presence of constitutive and inducible forms of NO synthase in human platelets. N omega-nitro-L-arginine, an inhibitor of NO synthase, potentiated thrombin-induced aggregation of washed human platelets, whereas L-arginine inhibited it. The direct evidence for the presence of constitutive form of NO synthase came from the observation of conversion of tritium-labeled L-arginine to tritium-labeled L-citrulline by washed platelets suspended in Ca(++)-rich but not in Ca(++)-free buffer. Incubation of washed platelets in Ca(++)-free buffer with cytokines (tumor necrosis factor-alpha and interferon-gamma) or cytokines plus lipopolysaccharide caused a marked increase in the conversion of [3H]L-arginine to [3H]L-citrulline, suggesting the presence of inducible form of NO synthase. Gel electrophoresis identified an approximately 130 kd protein band with NO synthase in the platelet cytosol, which on isolation converted [3H]L-arginine to [3H]L-citrulline. This 130 kd protein required the presence of Ca++, reduced nicotinamide adenine dinucleotide phosphate tetrahydro-L-biopterin, and flavin adenine dinucleotide for expression of NO synthase activity. Platelet sonicates demonstrated presence of nitrite, and its concentrations were lowered by preincubation of platelets with NG-nitro-L-arginine methyl ester and enhanced in cytokine-treated platelets. Reverse-transcription polymerase chain reaction demonstrated messenger RNA expression of the constitutive endothelial (but not brain) and inducible isoforms of NO synthase in platelets. These observations indicate that human platelet cytosol possesses both constitutive and inducible forms of NO synthase.
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PMID:Identification of constitutive and inducible forms of nitric oxide synthase in human platelets. 753 7


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