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)

The effect of endotoxic lipopolysaccharide (LPS) on platelet shape change (PSC; a preaggregation event) was investigated. PSC is accompanied by an increase in median platelet volume (MPV), which was measured using a channelyzer. In whole blood, but not in platelet rich plasma (PRP), LPS (final concentration 80 mg/l) caused an increase in MPV that could be detected for 2 h. When PRP (prepared from LPS- and saline-pretreated whole blood) was incubated for 40 min, the LPS-mediated increase in MPV could no longer be detected. Taken together, these data imply that PSC is both initiated and maintained by a labile factor(s) present in whole blood, but not in PRP. PRP was prepared from LPS-pretreated whole blood and incubated for 40 min to allow reversal of the LPS-induced PSC; further stimulation with LPS caused PSC. Platelets from LPS-pretreated whole blood also showed enhanced PSC with serotonin (5-HT), diminished PSC with platelet activating factor (PAF), and no change of response to ADP and collagen. Hence, LPS pretreatment of whole blood differentially alters responses of platelets to further stimulation with LPS and other agonists. A specific PAF antagonist completely abolished the effect of LPS on MPV. These data may contribute to an understanding of the cascading thrombotic events and thrombocytopenia associated with septicaemia.
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PMID:Platelet shape change in whole blood: differential effects of endotoxin. 809 94

The effects of E. coli lipopolysaccharide (LPS) on washed platelets of the healthy volunteers were studied by measuring ADP induced aggregation and intracellular ionized calcium concentration ([Ca2+]i) by fluorescent calcium indicator, quin 2. Addition of LPS in platelets suspension in saline, caused an increased platelet aggregation. Adding LPS, however, in platelet suspension in Na(+)-citrated platelet poor plasma inhibited ADP aggregation. These trends were not affected by cyclooxygenase inhibitor, but partially antagonized by dibutyryl cyclic AMP, and verapamil. The intracellular calcium ion concentration ([Ca2+]i) was significantly increased (334 +/- 141 nM to 150 +/- 45 nM in control) on addition of LPS in platelet suspension containing ionized calcium. On the other hand, there was no significant difference observed with those suspended in calcium free solution (50 +/- 16 to 45 +/- 15 in control). These results indicate that changes of platelet aggregation by LPS were mediated by cyclic AMP and Ca2+, but not by arachidate derivatives. The author concludes that LPS changed the mechanism of Ca2+ influx of platelet membrane and elevated [Ca2+]i of platelets. These findings, however, probably are not the cause of aggregation of platelets during DIC.
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PMID:[Effects of E. coli LPS on human platelet aggregation]. 818 78

Treatment of bone-marrow-derived macrophages with nanogram quantities of bacterial lipopolysaccharide (LPS) or with the synthetic bacterial lipopeptide analogue N-palmitoyl-(S)-[2,3-bis(palmitoyloxy)-(2RS)-propyl] (Pam3)Cys-Ala-Gly results in a change of ADP-ribosylation of a cytosolic 33 kDa protein. The immunostimulant-induced change is both dose- and time-dependent. It is not observed in macrophages from an LPS-unresponsive C3H/HeJ mouse strain upon treatment with LPS. Non-endotoxic LPS from Rhodopseudomonas pallustris, the inactive lipopeptide analogue Pam3CysOH, and LPS in the presence of polymyxin B fail to induce the change of ADP-ribosylation of the protein. These observations indicate that reversible protein modification by ADP-ribosylation might play a role in macrophage activation.
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PMID:Lipopolysaccharide-induced change of ADP-ribosylation of a cytosolic protein in bone-marrow-derived macrophages. 828 95

When monocytes are activated with endotoxin (lipopolysaccharide [LPS]), they make and release several mediators, including interleukin-1 beta (IL-1 beta). This study was undertaken to investigate the role of glucose in IL-1 beta production by these cells. IL-1 beta was produced in a dose-dependent manner to glucose concentration in the culture medium. The uptake of (3H)2-deoxyglucose in monocytes was stimulated by LPS 1,554% after 10 minutes, 6,095% after 2 hours, then gradually declined after 4 hours of incubation. The inhibition of the uptake of (3H)2-deoxyglucose by either 10 microM cytochalasin B or phloretin, added at the time of monocyte activation, was accompanied by significant reduction in ATP/ADP ratio and the inhibition of the production of IL-1 beta by activated monocytes. The synthesis of total protein did not change in monocytes activated in the absence of glucose in the culture medium, nor in the presence of either 10 microM cytochalasin B or phloretin. The export of IL-1 beta from LPS-activated monocytes was not inhibited by either 10 microM cytochalasin B or phloretin, nor in the absence of glucose in the culture medium. These data suggest that 1) glucose is required for LPS-induced IL-1 beta production by monocytes; 2) glucose is the major source of ATP for IL-1 beta production; 3) glucose transporter (GLUT 1) does not control the export of IL-1 beta.
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PMID:Role of glucose in interleukin-1 beta production by lipopolysaccharide-activated human monocytes. 840 38

The nitric oxide (NO) production by porcine aortic valve endothelial cells was estimated in cusps incubated at 37 degrees C by measuring their cyclic GMP content and the nitrite levels of the incubation medium. After a stabilization period, incubation for 5 min with acetylcholine, bradykinin, ADP and bovine thrombin resulted in a receptor-mediated increase in cyclic GMP which could be blocked by EGTA, N-omega-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA). Incubation with lipopolysaccharide (endotoxin) from E. coli O111:B4 or bovine for 5 h, dose-dependently increased nitrite production as well as cyclic GMP content. The elevated nitrite production was completely abolished in the presence of the protein synthesis inhibitor cycloheximide, was reduced by more than 50% by dexamethasone but was not affected by EGTA. L-NMMA dose-dependently reduced the increased nitrite production and cyclic GMP content. These results suggest that besides the presence of a constitutive NO synthase in porcine aortic valve endothelial cells thrombin, like lipopolysaccharide, triggers the de novo expression of an inducible Ca(2+)-independent NO synthase.
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PMID:Thrombin triggers the de novo expression of an inducible NO synthase in porcine aortic valve endothelial cells. 856 77

Stimulation of vascular smooth muscle with bacterial lipopolysaccharide (LPS) and proinflammatory cytokines induces the expression of a distinct isoform of NO synthase (inducible NOS [iNOS]) contributing to the suppression of vascular contractility. We have obtained evidence of the involvement of an indirect pathway triggered by NO and its reaction product peroxynitrite (ONOO-) through the activation of the nuclear enzyme poly-ADP ribosyltransferase (PARS) in the pathogenesis of cellular energetic and contractile failure in vascular smooth muscle. Exposure of vascular smooth muscle cells caused DNA strand breaks, activation of PARS, depletion of NAD+, and inhibition of mitochondrial respiration. The NAD+ depletion and inhibition of mitochondrial respiration were reduced by pharmacological inhibition of PARS. Stimulation of vascular smooth muscle cells with LPS and interferon gamma (IFN-gamma) triggered the production of superoxide anion over 3 to 48 hours and NO and ONOO- over 24 to 48 hours and resulted in significant DNA strand breakage. The decrease in mitochondrial respiration in response to LPS and IFN-gamma stimulation was inhibited by the ONOO- scavenger uric acid (100 mumol/L) and by inhibitors of iNOS. The PARS inhibitors 3-aminobenzamide (1 mmol/L), nicotinamide (1 mmol/L), and PD 128763 (100 mumol/L) inhibited the reduction in cellular NAD+ and ATP and the suppression of mitochondrial respiration in response to LPS and IFN-gamma stimulation. Administration of 3-aminobenzamide also reduced PARS activation and vascular hyporeactivity of rat thoracic aortas exposed to ONOO- (300 mumol/L to 1.5 mmol/L) in vitro. 3-Aminobenzamide (10 mg/kg IP) preserved the ex vivo contractility of aortas obtained from endotoxic rats and improved survival in lethal murine endotoxic shock. These data suggest that PARS activation due to iNOS induction (1) is involved in the energetic depletion of vascular smooth muscle cells that express iNOS and (2) contributes to the pathogenesis of vascular energetic and contractile failure in endotoxic shock. Inhibition of PARS may be a novel concept of therapeutic potential in shock.
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PMID:Role of poly-ADP ribosyltransferase activation in the vascular contractile and energetic failure elicited by exogenous and endogenous nitric oxide and peroxynitrite. 863 36

We have determined that gene HI#1181 of Haemophilus influenzae is a homolog of Escherichia coli gmhA (previously designated lpcA) (J. S. Brooke and M. A. Valvano, J. Biol. Chem. 271:3608-3614, 1996), which encodes a phosphoheptose isomerase catalyzing the first step of the biosynthesis of ADP-L-glycero-D-manno heptose. Mutations in this gene are associated with a heptoseless core lipopolysaccharide which determines an increased outer membrane permeability to hydrophobic compounds. The cloned H. influenzae gmhA restored the synthesis of a complete core in the gmhA-deleted E. coli strain chi711. Amino acid sequence comparisons of the GmhA proteins of E. coli and H. influenzae with other proteins in the databases revealed the existence of a novel family of phosphosugar a1do-keto isomerases.
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PMID:Molecular cloning of the Haemophilus influenzae gmhA (lpcA) gene encoding a phosphoheptose isomerase required for lipooligosaccharide biosynthesis. 865 17

Monophosphoryl lipid A (MLA), a derivative of the minimal substructure of lipopolysaccharide (lipid A) possesses immunomodulatory activity of the parent lipid A yet enjoys reduced toxicity. It has previously been reported that pretreatment with MLA reduces myocardial infarct size and stunning in dogs following ischemia and reperfusion. The aim of this study was to evaluate the ability of monophosphoryl lipid A (MLA) to preserve global cardiac function and peripheral hemodynamics in a rabbit model of prolonged regional ischemia (90 min), and reperfusion (6 h). An evaluation of potential mechanisms by which MLA may preserve cardiac function was also undertaken. Single dose pretreatment with MLA (35 micrograms/kg i.v.) 24 h prior to ischemia resulted in significant improvement in left ventricular developed pressure, dP/dt, rate-pressure product and mean arterial pressure during reperfusion (P < 0.05 v control). Although in this model of prolonged ischemia MLA pretreatment did not reduce infarct size (54.5 +/- 11.4% in control v 63.3 +/- 8.3% in MLA, P = N.S.), evaluation of myocardial adenylate and adenosine catabolite pools at the end of ischemia indicated a preservation of ATP and ADP and a decreased production of downstream adenosine catabolites including inosine, xanthine and uric acid. Adenosine kinase, but not 5'-nucleotidase (5'-NTase) or adenosine deaminase activity determined following reperfusion was 76% and 60% higher (P < 0.05) in non-risk and post-ischemic myocardium of MLA pretreated rabbits compared with controls. Although there was a trend toward lower tissue myeloperoxidase activity in post-ischemic myocardium from treated rabbits, the results were not significantly different from control animals. These results suggest that a 24-h pretreatment with MLA, without further treatment during ischemia or reperfusion was associated with: (1) preservation of global myocardial function during reperfusion; (2) preservation of myocardial high energy adenylates and reduced formation of adenosine catabolites during ischemia; (3) elevated myocardial adenosine kinase activity. Increased recycling of adenosine to phosphorylated nucleotides may result from MLA's affect on adenosine kinase, which could explain the drugs effect on adenylate and adenosine metabolite pools.
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PMID:Preservation of global cardiac function in the rabbit following protracted ischemia/reperfusion using monophosphoryl lipid A (MLA). 874 27

The aim of this work was to study whether a G-protein regulates lipopolysaccharide (LPS) induced TNF-alpha production in tumour-bearing rat peritoneal macrophages differently to in normal rats. We also investigated whether a state of 'early endotoxin tolerance' affects LPS induced TNF-alpha release via a G-protein-mediated phenomenon. LPS-stimulated (50 micrograms ml-1 of Salmonella enteritidis LPS) TNF-alpha release was investigated in peritoneal macrophages harvested from both normal rats and tumour-bearing rats. Cholera toxin (10, 100 and 1000 ng ml-1) did not significantly modify LPS-induced TNF-alpha release. In contrast pertussis toxin (0.1, 1.0 and 10 ng ml-1) significantly increased LPS-induced TNF-alpha release and inhibited LPS-stimulated prostaglandin E2 (PGE2) production in both normal rat macrophages and tumour-bearing rat macrophages. Pertussis toxin effects on these LPS responses were correlated with a pertussis-toxin-mediated ADP-ribosylation of a 41 kDa protein(s). The LPS-mediated responses were significantly greater in macrophages from tumour-bearing rats than in macrophages from normal rats. PGE2 (10(-9), 10(-8) and 10(-7) M) suppressed LPS-induced TNF-alpha production in a dose-dependent fashion. A state of 'early endotoxin tolerance' was then induced in tumour-bearing rats by a single intravenous injection of 125 micrograms rat-1 of LPS, and experiments were performed on peritoneal macrophages harvested 24 h after LPS injection. In tolerant macrophages pertussis toxin induced an increase in LPS-stimulated TNF-alpha release and an inhibition in LPS-stimulated PGE2 release significantly lower than in macrophages harvested from non-tolerant tumour bearing rats. Our results suggest that a pertussis-toxin-sensitive G-protein may serve to regulate the synthesis of TNF-alpha in rat peritoneal macrophages and that the activity of this pertussis-sensitive G-protein is increased in macrophages from tumour-bearing rats. Furthermore, our experiments would indicate that a 'state of endotoxin tolerance', caused by altering the function of presumably a Gi-protein, may exert beneficial effects on the functions of macrophages in tumour-bearing rats.
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PMID:Endotoxin tolerance impairs a pertussis-toxin-sensitive G-protein regulating tumour necrosis factor release by macrophages from tumour-bearing rats. 888 Aug 92

A recently recognized property of nitric oxide (NO), which would be expected to alter cell function, is the capacity to induce the ADP-ribosylation of various proteins. In these studies we demonstrate that actin present in murine macrophages is a substrate for NO-dependent ADP-ribosylation and that this modification is associated with the modification of cellular functions in murine peritoneal macrophages. A 42-kDa substrate for NO-dependent ADP-ribosylation was identified as actin by binding to DNAse-I and immunoprecipitation with anti-actin antibodies. The amount of actin ADP-ribosylation was correlated with the concentration of sodium nitroprusside (SNP), a NO generating agent, used in each experiment and with the amount of NO produced by activated macrophages. However, a specific inhibitor for NO synthase, N(G)-monomethyl-L-arginine (N(G)MMA), inhibited the ADP-ribosylation of actin by blocking the NO production in the interferon (IFN)-gamma plus lipopolysaccharide (LPS)-stimulated cells. Because the integrity of cytoskeletal protein is involved in shape change, adhesion, and phagocytosis of cells, we elucidated the role of NO-dependent ADP-ribosylation of actin in murine macrophages. A morphology kinetics assay comparing pseudopodial extension values over a 72-hr period showed that IFN-gamma plus LPS-treated macrophages underwent a wave of morphological changes, returning to a round shape after 32 hr. However, incubation of the cells with IFN-gamma plus LPS in the presence of N(G)MMA resulted in spindle-shaped pseudopodia formation and an altered composition of F-actin in macrophages. Adding either SNP or botulinum C2 toxin also inhibited IFN-gamma plus LPS-induced pseudopodia formation even in the presence of N(G)MMA. Flow cytometry revealed that NO inhibits the phagocytosis of fluorescent particles in a reversible manner. Preincubation of the cells with SNP (2 mM) also diminished LPS- or phorbol 12-myristate 13-acetate-induced macrophage adhesion on a laminin substratum. Collectively, in addition to its better-characterized role as a cytolytic mediator, the data illustrate that NO shows negative regulatory roles in cytoskeletal assembly, pseudopodia formation, phagocytosis, and adherence of murine macrophages in association with the ADP-ribosylation of actin.
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PMID:Nitric oxide induces ADP-ribosylation of actin in murine macrophages: association with the inhibition of pseudopodia formation, phagocytic activity, and adherence on a laminin substratum. 892 51


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