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 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

Bacterial lipopolysaccharide (LPS) initiates the cascade of inflammatory events that, in infected patients, often result in a lethal systemic inflammatory response known as the sepsis syndrome. We studied LPS-stimulated expression of tissue factor (TF) in human peripheral blood mononuclear cells (PBMCs) and cultured endothelial cells or tumor necrosis factor-alpha (TNF-alpha) in PBMCs. CD14, a PBMC membrane protein, is involved in LPS signaling and is also present as a soluble molecule in serum. CD14 is absent from endothelial cells and, in varying degrees, from monocytes of patients with paroxysmal nocturnal hemoglobinuria (PNH). LPS stimulation of TF in normal monocytes was enhanced > 30-fold by serum at low concentrations of LPS (< or = 10 ng/ml). The serum dependence of endothelial cells was even more pronounced; a full response to LPS was not observed in endothelium under serum-free conditions, even with LPS concentrations as high as 100 ng/ml. To better define the role of CD14, CD14-deficient PBMCs from two patients with PNH were compared with normal PBMCs. Although less than 3% of PNH monocytes expressed CD14, LPS-induced synthesis of TF and TNF-alpha by PBMCs from PNH patients was inhibited by anti-CD14 antibodies. Because patient serum samples were found to contain soluble CD14, we sought to determine whether PNH monocytes might respond to LPS through an activation pathway dependent on soluble CD14. Recombinant soluble CD14 substituted for serum to enable LPS stimulation of endothelium, PNH PBMCs, and surprisingly, CD14-replete normal PBMCs. In addition, a truncated sCD14 containing the N-terminal 152 amino acids similarly enabled LPS stimulation of normal PBMCs. These data underscore the importance of soluble CD14 and suggest that CD14 present in serum enables LPS responses in PNH monocytes and endothelial cells and may even influence the effects of LPS in normal human phagocytes.
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PMID:Soluble CD14 promotes LPS activation of CD14-deficient PNH monocytes and endothelial cells. 753 90

Tissue factor (TF) is the cellular receptor for factor VIIa. In complex with TF, factor VIIa initiates coagulation by activation of factor IX and factor X. TF is normally not in contact with blood, but is expressed on extravascular cells which forms a haemostatic envelope ready to activate coagulation when vascular integrity is disrupted. However, under pathological conditions monocytes, but probably not endothelial cells, are stimulated to express TF activity on the surface of the cells and may thereby trigger activation of blood coagulation. For several years we have observed some individuals (high responders) with a very high response to lipopolysaccharide (LPS) as judged by induction of TF activity in their monocytes in whole blood. This phenomenon has been shown to be mediated by a P-selectin dependent interaction between granulocytes, platelets and monocytes where the release of platelet factor 4 (PF4) plays an important role. It is concluded that cellular interactions play a central role in the expression of TF activity in circulating monocytes.
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PMID:Cellular interactions in tissue factor expression by blood monocytes. 754 63

Tissue factor (TF) is a transmembrane glycoprotein which assembles with factor VIIa on cell surfaces to form a proteolytically active cofactor-enzyme complex; the TF/VIIa complex initiates the coagulation protease cascade. In response to bacterial lipopolysaccharide (LPS) and phorbol-12 myristate 13-acetate (PMA), monocytes synthesize and express TF on their surface. However, the mechanisms by which LPS and PMA activate TF synthesis by human blood monocytes are not fully understood. As it has been established that LPS and PMA activate protein tyrosine kinase (PTK) in monocytes, we studied the role of PTK in LPS and PMA induction of TF by human blood monocytes. Both LPS- and PMA-induced TF activity was inhibited in a concentration-dependent manner by the protein tyrosine kinase-specific inhibitors herbimycin A and genistein. TF antigen determination confirmed that LPS- and PMA-induced cell surface TF protein levels decreased in parallel to TF functional activity under herbimycin A and genistein treatment. Northern blot analysis of total RNA from LPS- and PMA-stimulated monocytes showed a concentration-dependent decrease in TF mRNA levels in response to herbimycin A and genistein. The rate of decay of LPS-induced TF mRNA, evaluated after the arrest of transcription by actinomycin D was not affected by genistein and herbimycin A, suggesting that the inhibitory effects occur at least partly at the transcriptional level. We conclude that LPS- and PMA-induced TF production by human monocytes is dependent on tyrosine kinase activation.
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PMID:Protein tyrosine kinase activation is required for LPS and PMA induction of tissue factor mRNA in human blood monocytes. 754 19

We compared peritoneal dialysis effluents from 18 CAPD patients who had not suffered from peritonitis during the last 6 months (group 1) with the effluents from five patients with acute peritonitis (group 2), measuring activation markers of coagulation and fibrinolysis. These markers included prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT), fibrin monomer (FM), and fibrin degradation products (FbDP). In the dialysate of group 1 we found remarkably high levels of F1 + 2, TAT and FM concomitant with a high concentration of FbDP, indicating a high rate of intraperitoneal fibrin turnover. The balance between peritoneal generation and degradation of fibrin was disturbed in untreated patients of group 2, who had significantly higher levels of coagulation markers and a higher ratio between FM and FbDP. Seven days after treatment with intraperitoneal administration of antibiotics and heparin, F1 + 2, TAT, FM and FbDP decreased significantly. To evaluate the role of mesothelial cells (MC) in the high peritoneal fibrin turnover we investigated the expression of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor type-1 (PAI-1), and tissue factor in cultured human peritoneal MC under basal conditions and after exposure to tumour necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), or bacterial lipopolysaccharide (LPS). The exposure of MC to TNF alpha or to a lesser extent IL-1 alpha or LPS reduced their fibrinolytic activity by decreasing t-PA production and increasing PAI-1 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Imbalance between intraperitoneal coagulation and fibrinolysis during peritonitis of CAPD patients: the role of mesothelial cells. 756 82

The role of tissue factor (TF) as an initiator of the thrombotic complications secondary to atherosclerosis has been acknowledged, and in situ expression of TF activity by monocyte-derived macrophages and lesion-associated macrophage foam cells has been documented. Macrophages express TF activity upon exposure in vitro to either oxidized low density lipoprotein LDL (Ox-LDL) or endotoxin (lipopolysaccharide). This activity has been associated with membrane vesicles that apparently are shed after procoagulant expression. The present study based upon the correlative use of an enzyme-linked coagulant assay and three-dimensional multi-antigen, immunogold electron microscopy, reports the ultrastructural localization of TF antigen and spatially correlates TF with OX-LDL binding and the presence of nascent fibrin polymers on the plasma membrane of cultured macrophages. Pigeon monocyte/macrophages, after a 4-hour induction with lipopolysaccharide (2 micrograms/ml) or minimally oxidized LDL (50 micrograms/ml; thiobarbituric acid reducing substance, 5 to 8 nmol/mg protein) were incubated for 40 minutes in a Tris-buffered medium containing factors VII, V, X, II, and I before either assaying for coagulant activity or processing for gold-colloid cytochemistry. TF activity, as measured by enzyme-linked coagulant assay peaked 6 hours after agonist exposure with lipopolysaccharide and Ox-LDL giving, respectively, 115- and 60-fold stimulation as compared with control. This activity corresponded to the elaboration of membrane ruffles and microvilli on the cell surfaces. Through correlative immunogold cytochemistry (15-nm-diameter colloid) and gold-ligand cytochemistry (30-nm-diameter colloid), TF antigen (83%) and Ox-LDL (78%) were primarily associated with the membrane ruffles and microvilli. Multi-antigen immunogold cytochemistry when used in conjunction with ligand-gold cytochemistry documented co-localization of Ox-LDL (22-nm gold), TF antigen (15-nm gold) and a delicate three-dimensional network of short fibrin fibers that were decorated in a linear fashion with the immunogold probes (30-nm gold). These results provide evidence that TF antigen is located at selected regions on the cell surfaces. Furthermore, these same regions provide binding sites for agonist uptake and organization sites for fibrin polymerization. Hypothetically, the localized membrane regions could be shed from the cell surface as a means for regulating coagulation potential.
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PMID:Procoagulant activity after exposure of monocyte-derived macrophages to minimally oxidized low density lipoprotein. Co-localization of tissue factor antigen and nascent fibrin fibers at the cell surface. 757 48

In a previous study we have shown that granulocytes enhance lipopolysaccharide (LPS)-induced tissue factor (TF) activity in monocytes in a platelet-dependent reaction. The present investigation was undertaken to examine the role of a platelet activation product, platelet factor 4 (PF4), in LPS-induced TF activity in monocytes. Platelet lysate supernatant, purified PF4, and the COOH-terminal tridecapeptide of PF4, termed PF4(58-70), enhanced LPS-induced TF activity in monocytes of whole blood dose dependently. A monoclonal antibody against P-selectin eliminated the enhancing effect of PF4(58-70) on LPS-induced TF activity in monocytes, and PF4(58-70) was shown to act synergistically with tumor necrosis factor alpha (TNF-alpha). However, PF4(58-70) did not enhance TNF-alpha secretion in LPS-stimulated whole blood. The major effect of PF4(58-70) was granulocyte dependent. Our results suggest that PF4 might play an important role in LPS-stimulated monocyte TF activity of whole blood.
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PMID:A novel biological effect of platelet factor 4 (PF4): enhancement of LPS-induced tissue factor activity in monocytes. 759 59

Tissue factor (TF), a 46-kD glycoprotein receptor for coagulation factors VII and VIIa, is expressed on the surface of endothelial cells in response to a variety of agonists and is thought to play an important role in initiating the thrombosis associated with inflammation during infection, sepsis, and organ transplant rejection. The induction of TF activity by lipopolysaccharide (LPS) is regulated, at least partially, at a transcriptional level and an LPS response element containing two activator protein-1 sites and a nuclear factor-kappa B (NF kappa B)-like site has been localized to the 5' flanking region of the TF gene by transfection studies of TF promoter/reporter gene constructs. We have examined the effect of pyrrolidine dithiocarbamate (PDTC), a specific inhibitor of the NF kappa B pathway on the expression of the endogenous TF gene in human umbilical vein endothelial cells (HUVEC). Preincubation of HUVEC for 60 minutes with PDTC inhibited LPS induction of TF activity on the cell surface in a dose-dependent manner, with 50% inhibition occurring at 10 mumol/L PDTC and 100% inhibition at higher concentrations (> or = 100 mumol/L). Furthermore, PDTC inhibited TF expression in response to tumor necrosis factor-alpha, interleukin-1 beta, and phorbol 12-myristate 13-acetate. The effect of PDTC was at the mRNA level, as seen by the complete abrogation of the large increase in TF mRNA observed in LPS-treated HUVEC. These results suggest that endothelial cell activation by diverse agonists initiates intracellular signaling events that converge upon a common pathway involving NF kappa B and, furthermore, that NF kappa B activation is an obligatory step induction of TF.
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PMID:Pyrrolidine dithiocarbamate abrogates tissue factor (TF) expression by endothelial cells: evidence implicating nuclear factor-kappa B in TF induction by diverse agonists. 760 83

The tissue factor (TF) gene is expressed in a cell type-specific manner in vivo. It is constitutively expressed by several extravascular cell types and inducibly expressed within the vasculature by monocytes and endothelial cells. TF expression initiates thrombotic episodes associated with various diseases, including atherosclerosis, septic shock, and cancer. Regulatory elements within the human TF promoter have been identified by functional analysis of TF promoter-luciferase gene plasmids transiently transfected into various cell types. Transcription factors that control expression of the TF gene were identified using gel shift mobility assays. Induction of the TF gene in human monocytic cells and endothelial cells exposed to bacterial lipopolysaccharide or cytokines is mediated by a distal enhancer (-227 to -172 bp) containing two AP-1 sites and a kappa B site. Functional interactions between Fos-Jun heterodimers and c-Rel-p65 heterodimers are required for transcriptional activation of the TF gene. In contrast, serum and phorbol ester induction of the TF gene in human epithelial cells is controlled by a proximal enhancer (-111 to +14 bp) containing three overlapping Egr-1/Sp1 binding sites. Sp1 is constitutively expressed whereas Egr-1 expression is induced by serum or phorbol ester stimulation. Sp1 also mediates basal promoter activity. Thus, TF gene expression is complex and is regulated by a number of transcription factors that bind to distinct regions of the TF promoter.
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PMID:Regulation of the tissue factor gene. 761 58

Murine hepatitis virus strain (MHV-3) produces a strain-dependent pattern of disease which has been used as a model for fulminant viral hepatitis. This study was undertaken to examine whether there was a correlation between macrophage activation and susceptibility or resistance to MHV-3 infection. Peritoneal macrophages were isolated from resistant A/J and susceptible BALB/cJ mice and, following stimulation with MHV-3 or lipopolysaccharide (LPS), analyzed for transcription of mRNA and production of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), mouse fibrinogen-like protein (musfiblp), tissue factor (TF), leukotriene B4, and prostaglandin E2 (PGE2). Macrophages from BALB/cJ mice produced greater amounts of IL-1, TNF-alpha, TGF-beta, leukotriene B4, and musfiblp following MHV-3 infection than macrophages from resistant A/J mice, whereas in response to LPS, equivalent amounts of IL-1, TNF-alpha, TGF-beta, and TF were produced by macrophages from both strains of mice. Levels of mRNA of IL-1, TNF-alpha, and musfiblp were greater and more persistent in BALB/cJ than in A/J macrophages, whereas the levels and kinetics of IL-1, TNF-alpha, and TF mRNA following LPS stimulation were identical in macrophages from both strains of mice. Levels of production of PGE2 by MHV-3-stimulated macrophages from resistant and susceptible mice were equivalent; however, the time course for induction of PGE2, differed, but the total quantity of PGE2 produced was insufficient to inhibit induction of musfiblp, a procoagulant known to correlate with development of fulminant hepatic necrosis in susceptible mice. These results demonstrate marked differences in production of inflammatory mediators to MHV-3 infection in macrophages from resistant A/J and susceptible BALB/cJ mice, which may explain the marked hepatic necrosis and fibrin deposition and account for the lethality of MHV-3 in susceptible mice.
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PMID:Pattern of disease after murine hepatitis virus strain 3 infection correlates with macrophage activation and not viral replication. 763 67


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