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

When incubated with lipopolysaccharide (LPS) in the presence of plasma, neutrophils become primed for enhanced release of superoxide in response to triggering by formyl-Met-Leu-Phe (fMLP). The effect of LPS on phagocytes is inhibited by a synthetic lipid A precursor, LA-14-PP (lipid IVa) or by LPS from Rhodobacter sphaeroides (Rs). We studied the mechanisms by which LA-14-PP or Rs-LPS inhibited LPS-induced responses. When neutrophils were exposed to LA-14-PP or Rs-LPS for 3 min and then to Escherichia coli-LPS, the antagonists inhibited priming for superoxide release, and also blocked up-regulation of CD11b and adherence. This inhibition was dependent on plasma, was not overcome by higher amounts of E. coli-LPS or plasma, and was not observed at 0 degrees C, suggesting that E. coli-LPS was not able to interact with its receptor or other cellular recognition molecule in neutrophils that had been exposed to the antagonists. The alternative possibility that LA-14-PP or Rs-LPS depleted a plasma cofactor, resulting in inhibition of priming, was investigated by using LPS from Porphyromonas gingivalis (Pg) and Bordetella pertussis (Bp). These LPS primed neutrophils in a plasma-dependent and CD14-dependent manner, but were not blocked by LA-14-PP or Rs-LPS. When sub-optimal concentrations of plasma were exposed to LA-14-PP or Rs-LPS, and then mixed with Pg-LPS or Bp-LPS, followed by incubation with neutrophils, priming and up-regulation of CD11b were inhibited, and this inhibition was overcome by increasing the concentration of plasma. Binding of LPS-binding protein (LBP) in plasma to immobilized E. coli-LPS was inhibited by pre-incubation of plasma with LA-14-PP or Rs-LPS. Together with the result that treatment of plasma with anti-LBP antibody abolished the cofactor activity of plasma, these results indicated that LA-14-PP and Rs-LPS depleted LBP from plasma, resulting in inability of LPS to act on neutrophils. Thus LA-14-PP and Rs-LPS inhibited the action of LPS on neutrophils by at least two mechanisms, blocking of LPS receptor recognition and depletion of the cofactor LBP.
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PMID:An analogue of lipid A and LPS from Rhodobacter sphaeroides inhibits neutrophil responses to LPS by blocking receptor recognition of LPS and by depleting LPS-binding protein in plasma. 749 65

Rat microglia in culture showed a high capacity to degrade neuropeptides compared with other glial cells. Leu-enkephalin was readily hydrolyzed to free tyrosine and Gly-Gly-Phe-Leu. Inhibition experiments and immunostaining revealed that aminopeptidase N (CD13) on the surface of microglia was responsible for enkephalin cleavage. Endopeptidase-24.11 ("enkephalinase"), angiotensin-converting enzyme, or carboxypeptidases could not be detected on microglia. Aminopeptidase N activity in microglia was considerably higher than in rat peripheral monocytes and macrophages, which both also exhibited low endopeptidase 24.11 activities. Activity of aminopeptidase N was upregulated by culture of microglia on astrocytes and down-regulated by exposure of microglia to lipopolysaccharide. The occurrence of aminopeptidase N on microglia is in line with the view that they originate from the monocytic lineage.
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PMID:Enkephalin metabolism by microglial aminopeptidase N (CD13). 753 37

Helicobacter pylori is important in the aetiology of peptic ulceration. Despite inducing an inflammatory response in the mucosa, the organism persists, suggesting that it has efficient protective mechanisms. Some bacterial and viral products modulate histamine secretion from inflammatory cells. Therefore, this study examined the modulatory effects of H. pylori preparations on histamine release from rat peritoneal mast cells and human basophils. Eleven clinical isolates of H. pylori were prepared in different ways: as whole washed bacteria, washed sonicated bacteria, and formalin-killed bacteria, and as outermembrane and lipopolysaccharide (LPS) extracts. Histamine release from mast cells or basophils was not elicited by any of these bacterial preparations alone. However, when mixed with various secretory stimulants, the bacterial preparations caused inhibition of histamine release from rat mast cells (calcium ionophore A23187, compound 48/80, concanavalin A, anti-rat IgE) and human basophils (A23187, N-formyl Met-Leu-Phe). The degree of inhibition ranged from 48% to 97%. These results indicate that H. pylori exerts an inhibitory effect on cells of the immune system that contributes to its persistence within the gastric mucosa.
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PMID:Modulatory action of Helicobacter pylori on histamine release from mast cells and basophils in vitro. 754 Jun 93

The role of both endotoxin and neutrophils in the development of acute lung injury continues to be debated. We hypothesized that early in the course of the development of the adult respiratory distress syndrome (ARDS) circulating neutrophils could be primed by endotoxin and that subsequent stimulated responses could be enhanced. Accordingly, neutrophils were isolated from patients at risk for and with ARDS. Unstimulated neutrophils from these patients neither produced nor were primed for superoxide production. Whereas phorbol myristate acetate-stimulated superoxide production was preserved, indicating that the cells were capable of a response, patient neutrophils produced less superoxide than did cells from normal subjects when primed with endotoxin (lipopolysaccharide [LPS]) and stimulated with formyl-methionyl-leucine-phenylalanine (FMLP), suggesting that there was a defect in the signal transduction mechanism for LPS. This was confirmed by the finding that patient neutrophils also had both decreased baseline CD14 expression and less CD14 upregulation after LPS stimulation compared with neutrophils from normal subjects. The mechanisms that could account for the decreased CD14 expression were studied in vitro. Neutrophils from normal subjects both upregulate CD14 in response to LPS and shed CD14 over time, suggesting that in patients CD14 receptors could have been previously upregulated and shed. In addition, there is an association between CD14 expression and retention such that normal LPS-stimulated neutrophils which are not retained in a filtration system have decreased CD14 expression. Thus, in patients, those PMN most responsive to LPS could be preferentially sequestered and not available in the circulation for study.
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PMID:Neutrophil response to endotoxin in the adult respiratory distress syndrome: role of CD14. 754 95

Pertussis toxin (Ptx) is a hexameric protein with classical AB architecture produced by Bordetella pertussis. The aim of this study was to investigate the effect of Ptx on migration of polymorphonuclear leukocytes to site of inflammation and on cell-dependent edema. Ptx was purified from the supernatant of the culture medium of B. pertussis using hydroxylapatite chromatography and fetuin affinity chromatography. Ptx induced a maximal clustering of Chinese hamster ovary cells at concentrations as low as 0.1 ng/ml. Intravenous injection of Ptx (400 ng) significantly blocked the neutrophil migration induced by 200 ng of lipopolysaccharide (LPS from E. coli O111:B4; 2.27 +/- 0.13 vs 0.61 +/- 0.16 per 10(6) neutrophils/ml; P < 0.001; N = 5) and by 200 ng of formyl-methionyl-leucyl-phenylalanine (fMLP; 2.53 +/- 0.45 vs 0.75 +/- 0.14 per 10(6) neutrophils/ml; P < 0.01; N = 6) into the peritoneal cavities of male Wistar rats (weighing 150-180 g). In addition, Ptx (400 ng) pretreatment also blocked the edema induced by intraplantar injection of 100 micrograms carrageenin (delta increase in volume: 0.667 +/- 0.087 vs 0.313 +/- 0.058 ml; P < 0.01; N = 5) but not the edema induced by 100 micrograms dextran (delta increase in volume: 0.537 +/- 0.06 vs 0.385 +/- 0.076 ml; P > 0.05; N = 5). These data demonstrate that Ptx blocked neutrophil migration induced by a direct fMLP stimulus of a site of inflammation. In addition, this toxin blocks the indirect stimulus of LPS on neutrophil migration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pertussis toxin from Bordetella pertussis blocks neutrophil migration and neutrophil-dependent edema in response to inflammation. 758 Oct 20

The prevailing view of neutrophil NADPH-oxidase activation during interaction with bacteria is that the production of toxic oxygen metabolites should be directed into the phagosome containing the engulfed prey. However, in this report we show that a common Escherichia coli strain, HB101, may induce a release of neutrophil oxygen metabolites to the extracellular milieu. This phenomenon is dependent on three factors: (i) the mobilization (upregulation) of neutrophil secretory vesicles prior to interaction with the bacteria, (ii) soluble bacterial factors binding to the formylmethionyl-leucyl-phenylalanine receptor and tentatively identified as formylated peptides, and (iii) a bacterium-associated priming factor identified as lipopolysaccharide.
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PMID:Escherichia coli-induced activation of neutrophil NADPH-oxidase: lipopolysaccharide and formylated peptides act synergistically to induce release of reactive oxygen metabolites. 759 Nov 13

We have shown previously that guinea pig alveolar macrophages (AM) synthesize a secretory phospholipase A2 (PLA2) during in vitro incubation. Here, we report the molecular cloning of this enzyme and show that it has structural features closely related to all known mammalian type-II PLA2. The mRNA and PLA2 activity were undetectable in freshly collected AM, but their levels increased dramatically to reach maximal values after 16 h of culture. Thereafter, the PLA2 activity remained constant with a parallel secretion in the medium, in contrast to mRNA level which returned to near basal values after 32 h. Incubation of AM for 16 h with the inflammatory secretagogue peptide f-Met-Leu-Phe (fMLP) markedly reduced the PLA2 activity and mRNA levels. This inhibition was prevented by preexposure of AM to pertussis toxin, an inhibitor of G-protein. In contrast, when AM were first cultured for 16 h and then incubated with fMLP, no significant change was observed in their PLA2 activity. In conditions where the type-II PLA2 was completely abrogated by fMLP, the latter did not alter the lipopolysaccharide-induced accumulation of tumor necrosis factor alpha mRNA or the release of arachidonic acid induced by the subsequent addition of the calcium ionophore A23187. These studies show that the inflammatory peptide fMLP down-regulates the expression of the type-II PLA2 by AM through a process mediated by G-protein. A possible negative control of the type-II PLA2 expression during AM activation is suggested.
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PMID:Expression of the type-II phospholipase A2 in alveolar macrophages. Down-regulation by an inflammatory signal. 761 34

Non-activated neutrophils strongly adhere to cytokine-activated human umbilical vein endothelial cells (HUVE). However, activation of neutrophils by different chemotactic mediators led to potent inhibition of this endothelial-dependent interaction. For different formylated peptides, concentrations leading to maximal adherence inhibition coincided with those known for inducing maximal chemotactic migration of neutrophils. In terms of maximal adherence inhibition, a rank list was found in the order of N-formyl-Met-Leu-Phe > C5adesArg > interleukin-8 > C5a > or = leukotriene B4, whereas platelet-activating factor, and lipopolysaccharide showed no inhibition. This rank order was congruent to that of down-regulation of neutrophil L-selectin detected by the monoclonal antibody Leu-8. Moreover, the dose-dependent increase of neutrophil adherence inhibition corresponded to the loss of L-selectin expression. Concentrations higher than that required for maximal inhibition led to a dose-dependent decrease of inhibition, which was accompanied by increasing expression of neutrophil CD11/CD18. In contrast to the capacity of non-activated neutrophils to migrate across interleukin-1-activated HUVE monolayers, transmigration was significantly impaired after chemotactic activation.
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PMID:Chemotaxins inhibit neutrophil adherence to and transmigration across cytokine-activated endothelium: correlation to the expression of L-selectin. 768 53

The addition of fMet-Leu-Phe or phorbol 12-myristate 13-acetate to human neutrophils stimulates phospholipase D activity as evidenced by the release of phosphatidic acid and the generation of diacylglycerol, and in the presence of ethanol the formation of phosphatidyl ethanol. The activation of phospholipase D by either the chemotactic factor or active phorbol ester is inhibited by the tyrosine kinase inhibitor erbstatin. The fMet-Leu-Phe-induced stimulation of this enzyme is greatly potentiated in cells which have been preincubated with low concentrations of lipopolysaccharide and serum. The presence of serum is essential for the potentiation by low concentrations of lipopolysaccharide. Moreover, the monoclonal antibody MY4(IgG2b) against CD14 inhibits the potentiation by the low concentration of lipopolysaccharide. These data suggest three important points. First, a tyrosine kinase step is necessary for the activation of phospholipase D. This suggests that the phospholipase D enzyme needs to be phosphorylated on tyrosine residues to be activated. Second, low concentrations of lipopolysaccharide, in the presence of serum, can potentiate the stimulated activity of this enzyme. Third, the priming action of the lipopolysaccharide-serum complex is mediated by CD14.
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PMID:Lipopolysaccharide in combination with serum potentiates the stimulated activity of phospholipase D in human neutrophils via CD14. 768 89

Stimulation of heparinized blood with 1 microM formyl-methionyl-leucyl-phenylalanine (FMLP) resulted in the formation of < 30 pmol/ml plasma of 5-lipoxygenase (5-LO) products. The preincubation of blood with 1 microgram/ml of lipopolysaccharide (LPS) (Escherichia coli 0111-B4) for 30 min before stimulation with FMLP resulted in the accumulation of 250-300 pmol of 5-LO products per ml plasma. The major products detected were leukotriene B4 and (5S)-hydroxy-6,8,11,14-eicosatetraenoic acid which were produced in equivalent amounts. The priming activity was detectable with as little as 1-10 ng LPS per ml blood and was optimal using 1-10 micrograms LPS/ml blood. The priming for 5-LO product synthesis was optimal after 20-30 min of preincubation with LPS and declined at preincubation times > 30 min. The priming effect of LPS was also observed using the complement fragment C5a or interleukin 8 as agonists. Polymorphonuclear leukocytes (PMN) and peripheral blood mononuclear cells accounted for 80 and 20% of the synthesis of 5-LO products, respectively. The ability of LPS to prime isolated PMN was dependent on the presence of plasma and was inhibited by the anti-CD14 antibody IOM2, indicating a CD14-dependent priming mechanism. The priming of whole blood with tumor necrosis factor alpha (TNF-alpha) and LPS was additive and the presence of mononuclear cells did not enhance the ability of LPS to prime PMN, indicating that the priming activity of LPS is independent of LPS-induced TNF-alpha synthesis. The mechanism by which LPS enhance 5-LO product synthesis in PMN was investigated. Treatment of PMN with LPS strongly enhanced the release of arachidonic acid after stimulation with FMLP. The release of arachidonic acid was optimal 2-3 min after stimulation with FMLP, attaining levels 5-15-fold greater than those observed in unprimed cells stimulated with FMLP. These results demonstrate that LPS dramatically increases the ability of blood to generate 5-LO products, and support the putative role of leukotrienes in pathological states involving LPS.
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PMID:Lipopolysaccharides prime whole human blood and isolated neutrophils for the increased synthesis of 5-lipoxygenase products by enhancing arachidonic acid availability: involvement of the CD14 antigen. 769 Aug 33


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