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

Thioglycollate-induced peritoneal exudate cells (TG-PEC) developed increased procoagulant activity after incubation with lymphokine and lipopolysaccharide (LPS). Dilutions of up to 1/1000 for insoluble Con A and 1/200 for periodate-induced lymphokine supernatants were active in enhancing macrophage procoagulant activity (MPCA), which was detected after a 2-hr incubation period and steadily increased over 20 hr. MPCA could also be induced by antigen; peritoneal cells from sensitized B6AF1 mice with strong footpad reactions to ovalbumin (OVA) responded to as little as 0.1 microgram/ml OVA in the MPCA test in an antigen-specific manner. By contrast, PEC from sensitized CBA/J mice that gave poor in vivo responses to OVA only reacted with high concentrations of the antigen in vitro. Production of the lymphokine responsible for induction of MPCA required an Ly-1+2- T cell, a nylon wool-adherent cell, and an la-17-bearing adherent cell. The MPCA induced by lymphokine or LPS did not appear to be a serine esterase and was not inhibited by phospholipase C. Coagulation of human factor-deficient plasma with activated TG-PEC indicated a requirement for Factor X.
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PMID:Macrophage procoagulant activity as a measure of cell-mediated immunity in the mouse. 618 99

The synthesis and secretion of prostaglandins and leukotrienes by mouse peritoneal macrophages is under several regulatory controls. Arachidonic acid must first be released from phospholipid stores by the action of phospholipases. Macrophages have the capacity to deacylate arachidonic acid directly from the SN2 position of phospholipids via the action of a phospholipase A2. In addition, these cells contain a phospholipase C capable of removing inositol-phosphate from phosphatidylinositol generating diacylglycerol. Another enzyme, diacylglycerol lipase is present to then generate arachidonic acid. The free arachidonic acid then enters the cyclooxygenase pathway to generate prostaglandins, the lipoxygenase pathway to generate leukotrienes or both pathways. The nature of the inflammatory stimulus added to these cells determines which of the above pathways become operative. Zymosan and the Ca++ ionophore, A23187 stimulate the synthesis of both prostaglandins and leukotrienes whereas phorbol myristate acetate and lipopolysaccharide induce only the synthesis of prostaglandins. In addition, the synthesis of these two products by macrophages can be regulated by certain antiinflammatory compounds. Indomethacin, aspirin, ibuprofen and benoxaprofen are only inhibitors of the prostaglandin pathway, whereas BW755C, 5,8,11-ETYA, NDGA and sulindac sulfide (high doses) are inhibitors of the synthesis of both prostaglandins and leukotrienes. Dapsone, an effective drug for leprosy, also inhibits the synthesis of both of these products.
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PMID:Physiological and pharmacological regulation of prostaglandin and leukotriene production by macrophages. 632

The effect of bacterial exotoxins and endotoxins on phagocytosis was tested on human macrophages in monolayer cultures by determining the rate of zymosan particle ingestion at different toxin concentrations and incubation times. The exotoxins tested were staphylococcal alpha-toxin and diphtheria-toxin. The endotoxins used were lipopolysaccharides from Salmonella typhi, Salmonella typhimurium, Shigella flexneri and Serratia marcescens. Phagocytosis was significantly impaired after prolonged incubation with diphtheria toxin whereas alpha-toxin was ineffective. Endotoxin-treated macrophages showed a wide range of phagocytic activity. Enhancement of phagocytosis was observed with a low concentration of endotoxin (1 microgram/ml) from S. typhi, S. typhimurium and S. flexneri. Higher concentrations (2.5 and 5 micrograms/ml) depressed phagocytosis to varying extents, except for S. typhi lipopolysaccharide, which did not induce a significant decrease in phagocytosis in comparison to the controls.
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PMID:The influence of bacterial exotoxins and endotoxins on the phagocytic activity of human macrophages in culture. 635 Jan 91

The nature of the binding sites for lipopolysaccharide (LPS) on human monocytes was investigated using fluorescein isothiocyanate (FITC)-labelled LPS from Salmonella minnesota R595 (ReLPS). In the absence of serum, ReLPS bound to monocytes and this interaction was trypsin sensitive. A concentration of 0.1 mg/ml resulted in a 90% loss of LPS binding, while low concentrations increased this binding. Trypsin-treated monocytes recovered FITC-ReLPS binding after 20 hr culture, which was abrogated in the presence of cycloheximide and actinomycin D. This showed that de novo protein and mRNA synthesis were essential. A number of different proteins have been implicated in cellular binding of LPS to monocytes. In this paper we show that CD14 is not involved in direct binding of FITC-ReLPS to monocytes, since anti-CD14 monoclonal antibody (mAb) (3C10) and removal of most of cell-surface CD14 by phosphatidylinositol-specific phospholipase C did not prevent FITC-ReLPS binding. Furthermore, LPS also bound to CD14-deficient cells from a patient with paroxysmal nocturnal haemoglobinuria (PNH). FITC-ReLPS binding was not mediated by the CD11/CD18 complex since mAb to the alpha and beta chains of the CD11/CD18 complex did not alter the binding of FITC-ReLPS to cells. These observations indicate that ReLPS may interact with monocyte membrane protein(s) in the absence of serum. This binding site(s) for LPS might be different from those previously described by others.
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PMID:Serum-independent binding of lipopolysaccharide to human monocytes is trypsin sensitive and does not involve CD14. 750 49

Murine macrophages activated by interferon (IFN)-gamma and bacterial lipopolysaccharide (LPS) produce large amounts of nitric oxide (NO), which is a critical mediator for a variety of biological functions. The expression of this inducible NO synthase (iNOS) involves a protein kinase C (PKC)-dependent pathway, but the mechanism for the PKC activation in this system is unclear. Through analysis of diacylglycerol (DAG) synthesis and choline metabolism in activated macrophages, direct evidence is provided that NO synthesis involves the activation of an unusual phosphatidylcholine-specific phospholipase C (PC-PLC) and not a phosphatidylinositol-specific phospholipase C (PI-PLC) or phospholipase D (PLD).
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PMID:The role of a phosphatidylcholine-specific phospholipase C in the production of diacylglycerol for nitric oxide synthesis in macrophages activated by IFN-gamma and LPS. 751 Sep 53

Several monoclonal antibodies directed against the human CD14 antigen have been established. We now report that the antibody My4, but not LeuM3, reacts with porcine monocytes. Among porcine peripheral blood mononuclear cells (PBMC), 14.6% of the cells stain with the CD14 antibody My4, which is similar to the percentage obtained with the antiporcine monocyte antibody 74-22-15. Two-colour immunofluorescence reveals that My4 and 74-22-15 antigens are coexpressed on the same cells, and cell sorter-purified My4+ cells exhibit the morphology of monocytes. Whole blood analysis (which also shows staining of granulocytes) reveals that the average percentage of My4+ monocytes amongst all leucocytes is 5.8% with 580 cells/microliters. Furthermore, porcine peritoneal macrophages (PM) and alveolar macrophages (AM), both stain for My4, with a four-fold lower level on AM. Treatment of cells with phosphatidylinositol-specific phospholipase C decreases My4 staining, but does not affect staining with antibody 74-22-15. Immunoprecipitation with the My4 antibody from surface labelled pig mononuclear cells demonstrates a 54 kDa band similar to human CD14, and Western blotting with pig serum demonstrates two bands similar to the alpha and beta forms of human soluble CD14. Finally, the My4 antibody is capable of blocking lipopolysaccharide- (LPS)-induced interleukin-6 production in isolated PBMC. These data show that the My4 antibody recognizes genuine CD14 on porcine monocytes and macrophages.
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PMID:The antibody MY4 recognizes CD14 on porcine monocytes and macrophages. 752 41

The membrane-associated CD14 receptor (mCD14) is a monocyte/macrophage differentiation antigen, and it has been demonstrated to serve as a receptor for bacterial lipopolysaccharide (LPS; endotoxin). Binding of LPS to mCD14 has been shown to be associated with LPS-induced macrophage, monocyte, and neutrophil activation in humans. In this report, we describe the presence and function of an mCD14-like receptor on bovine alveolar macrophages (bAM). An immunofluorescence technique and flow cytometric analysis indicated binding of anti-human CD14 monoclonal antibodies (MAb) My4, 3C10, and 60bd to bAM. Binding of anti-CD14 MAb (3C10 and MY4) was reduced over 20% by pretreatment of bAM with phosphatidylinositol-specific phospholipase C (0.5 to 1.0 U/ml), indicating that bovine mCD14 is a glycosyl phosphatidylinositol-anchored protein. In addition, pretreatment of bAM with anti-CD14 MAb decreased binding of 125I-labeled LPS to macrophages, suggesting that bovine mCD14 serves as a receptor for LPS. A cDNA probe based on the human sequence for CD14 was used in Northern (RNA) blot analysis, and hybridization to human monocyte CD14 yielded the expected 1.5-kb band. Hybridization to bovine mRNA yielded a 1.5-kb band plus an unexpected 3.1-kb band. Constitutive expression of bovine CD14 mRNA was observed, and the expression level was modestly elevated in bAM stimulated for 24 h with LPS (1 ng/ml) in the presence of bovine serum. The function and activation of bAM were assessed by quantitation of tissue factor (TF) expression on the cells using an activated factor X-related chromogenic assay and S-2222 substrate. LPS (1 ng/ml)-mediated upregulation of TF expression on bAM was dependent on the presence of bovine serum components, and TF expression was inhibited by anti-CD14 MAb. In addition, TF mRNA levels in LPS-stimulated bAM were decreased by pretreatment of cells with anti-CD14 MAb (MAb 60bd, 10 micrograms/ml).
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PMID:CD14 and tissue factor expression by bacterial lipopolysaccharide-stimulated bovine alveolar macrophages in vitro. 752 35

1. The synthesis of nitric oxide (NO) by immune-stimulated murine phagocytic cells (J774) and the modulation of this synthesis by tricyclodecan-9-yl-xanthogenate (D609), a specific inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), was investigated. D609 dose-dependently suppressed production of NO, as measured by the release of nitrite and nitrate, in response to lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) in intact cultured cells with an IC50 of approximately 20 micrograms ml-1. D609 at 40 micrograms ml-1 completely abrogated immune-stimulated nitrite production. 2. The inhibitory effects of D609 on nitrite production were time-dependent and restricted to the first 18 h post-stimulation. D609 did not inhibit nitrite production in the cytosol of immune-stimulated phagocytes. 3. These findings indicate that the xanthogenate, D609, is a potent inhibitor of the induction of NO-synthase activity in immune-stimulated phagocytes. Furthermore, since D609 has been demonstrated to inhibit PC-PLC specifically, our findings suggest that the activation of this enzyme by LPS and IFN-gamma is a proximal step in the signal transduction of inducible NO-synthase in phagocytic cells.
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PMID:Induction of nitric oxide synthase activity in phagocytic cells inhibited by tricyclodecan-9-yl-xanthogenate (D609). 753 78

In human monocytes, superoxide (O2-) generation accompanies phagocytosis and is important for bactericidal activity. It also contributes to tissue damage in inflammation. In the present study we investigated, whether lipopolysaccharide (LPS) directly stimulates monocyte O2- production with kinetics known for other LPS effects and, if so, by which mechanism. LPS caused a time- and dose-dependent O2- release in nonadherent purified monocytes. The effect appeared after 5 min, peaked at 30 min, and disappeared after 2 h. It was maximal with 10 ng/ml lipid A (+148 +/- 22%, P < .001), 1 ng/ml LPS Escherichia coli Re (+226 +/- 68%, P < .001), and 100 ng/ml LPS Salmonella abortus equi sm (+272 +/- 52%, P < .001), respectively. The effect was not observed in buffer, even when using 10 micrograms/ml LPS. It was dependent on the presence of heat-inactivated AB serum, with a maximal effect at > or = 0.5%. Serum could be replaced by LPS-binding protein (LBP). Polymyxin B and anti-LBP antiserum, respectively, blocked the LPS effect. LPS-induced O2- generation was also completely blocked by anti-CD14 antibodies (3C10 and 63D3) and by their corresponding F(ab')2 fragments. Monocytes treated with phosphoinositol-specific phospholipase C and monocytes from patients with paroxysmal nocturnal hemoglobinuria, lacking the phosphatidylinositol-anchored CD14, did not respond to LPS stimulation with O2- production. Similarly to LPS, E. coli caused stronger O2- production with heat-inactivated serum than without, and this effect was blocked by anti-CD14 antibodies. In conclusion, these data indicate that LPS directly stimulates O2- production in human monocytes via CD14 depending on LBP.
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PMID:LPS directly induces oxygen radical production in human monocytes via LPS binding protein and CD14. 753 19

We have previously isolated a lipopolysaccharide (LPS)-resistant mutant (named LR-9) of a cultured macrophage-like cell line, J774.1. This mutant had defective LPS binding [Hara-Kuge, S., Amano, F., Nishijima, M., and Akamatsu, Y. (1990) J. Biol. Chem. 265, 6606-6610]. In this study, we found that: (1) LPS-binding to parental J774.1 cells was dependent on a serum factor with a molecular weight of about 60 kDa, probably LPS binding protein (LBP); (2) LPS-binding to J774.1 cells was markedly reduced by treating the cells with phosphatidylinositol-specific phospholipase C (PI-PLC); (3) mutant LR-9 cells were defective in LPS-binding even in the presence of serum; (4) LR-9 cells lacked CD14 protein on flow cytometric and immunoblot analyses, but retained normal CD14 mRNA levels on RNA blot analysis; (5) small amounts of LPS (1 to 10 ng/ml) activated J774.1, but not LR-9 cells, to secrete tumor necrosis factor-alpha and to release arachidonate metabolites, whereas both J774.1 and LR-9 were activated by large concentrations of LPS (100 to 1,000 ng/ml). These results provide genetic evidence that CD14 molecules in J774.1 cells play a crucial role in LPS-binding and in LPS-triggered signal transduction, and indicate that large amounts of LPS can activate J774.1 cells without the participation of CD14 molecules.
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PMID:Identification of a biochemical lesion, and characteristic response to lipopolysaccharide (LPS) of a cultured macrophage-like cell mutant with defective LPS-binding. 753 58


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