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 monocyte is the only circulating cell type capable of initiating blood coagulation by the expression of tissue factor (TF). The mechanism and kinetics of TF mRNA and TF activity induction in human peripheral blood monocytes (HPBM) in response to bacterial lipopolysaccharide (LPS) and phorbol myristate acetate (PMA) were investigated. Northern blot analysis showed that both LPS and PMA induce a transient accumulation of TF mRNA in HPBM, that reaches maximum levels after 3-6 h and rapidly declines thereafter. Nuclear run-on experiments demonstrated that the accumulation of TF mRNA requires de novo transcription of the TF gene. Since cycloheximide alone also caused an increase of TF mRNA levels and gene transcription it is concluded that the transcriptional activation of the TF gene does not require protein synthesis. Using specific protein kinase inhibitors, it was further demonstrated that activation of the protein kinase C pathway is involved in the induction of TF mRNA in HPBM. The accumulation of TF mRNA in LPS-stimulated HPBM is followed by an increase of TF activity on the cell surface. The kinetics of TF mRNA induction were found to be very similar in HPBM stimulated with LPS or PMA. However, in the latter case TF activity appeared considerably later on the cell membrane than in the LPS-stimulated cells. Non-stimulated HPBM contain very low levels of mRNA of the tissue factor pathway inhibitor (TFPI). No induction of TFPI (mRNA, activity or antigen) in HPBM after LPS or PMA treatment was demonstrated. This seems to be in contrast with the earlier observation that the human monocyte cell line U937 produces significant amounts of TFPI in response to treatment with LPS and PMA.
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PMID:Expression of tissue factor and tissue factor pathway inhibitor in monocytes in response to bacterial lipopolysaccharide and phorbolester. 805 53

An experimental disseminated intravascular coagulation (DIC) was induced in female CD rats by the intravenous administration of living bacteria (9.5 x 10(7) cfu Klebsiella pneumoniae), sublethal (5 mg/kg) or lethal (50 mg/kg) lipopolysaccharide (LPS), or tissue factor (1.5 micrograms/kg i.v. bolus or 0.4 micrograms/kg x hr i.v. infusion). We used a new fibrin monomer (FM) assay to follow the course of DIC. FM were detected by their ability to stimulate the tissue-type (t-PA) plasminogen activator dependent conversion of plasminogen to plasmin by a chromogenic assay. Miniplasminogen was used instead of plasminogen to avoid interference of the assay by alpha 2-antiplasmin. As a marker of DIC, elevated levels of FM were observed with all DIC-inducing agents (plasma levels were up to 90 micrograms/ml). The kinetics of FM formation were similar to the course of thrombin-antithrombin III (TAT) levels (maximal plasma levels 70 ng/ml); however, in the bacterial infection group, both parameters rose after a lag phase of about 1 hr. A 4 hr infusion of the highly specific thrombin inhibitor recombinant (rec.) hirudin (0.125 mg/kg x hr) resulted in a decrease of FM levels from 89.2 +/- 14.4 micrograms/ml in the LPS group (n = 10) to 27.4 +/- 11.2 micrograms/ml in the rec. hirudin group (n = 10; P < 0.001). The respective values for TAT levels were 73.1 +/- 19.7 micrograms/ml in the LPS group and 52.7 +/- 15.7 ng/ml in the rec. hirudin group (P < 0.001). Other coagulation parameters, such as platelets, fibrinogen, and fibrin(ogen) degradation products, were ameliorated accordingly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Formation of fibrin monomers in experimental disseminated intravascular coagulation and its inhibition by recombinant hirudin. 805 64

Increased procoagulant activity of vascular endothelial cells may be an important component in the pathogenesis of intravascular coagulation associated with gram-negative bacterial diseases. Two bovine endothelial cell (BEC) lines isolated from pulmonary arteries (ENS-2 and ENT-18) were used in this study to investigate procoagulant signal transduction pathways of endotoxin (lipopolysaccharide, LPS)--stimulated BECs. The endothelial cell line ENS-2 was sensitive to LPS as demonstrated by tissue factor (TF) expression, but in contrast, the ENT-18 endothelial cell line was unusually resistant to the effects of LPS. No remarkable quantitative difference in binding of radiolabeled LPS was detected between the two endothelial cell lines. A protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate, PMA) failed to induce TF expression in either cell line at concentrations ranging from 0.05 to 1.00 microM when used as a sole stimulus for the endothelial cells. However, when PMA was used in combination with LPS, PMA enhanced the stimulatory effect of LPS on the endothelial cells. In parallel experiments, PKC inhibitors (H-7 and GF 109203X) interfered with the stimulatory effect of LPS on the cells by decreasing tissue factor expression. We also found that an activator of adenylate cyclase, forskolin, similarly inhibited LPS-induced tissue factor activity. In contrast, protein tyrosine kinase inhibitors (genistein, lavendustin A) had no inhibitory effect on LPS-induced endothelial cell tissue factor expression. Our results collectively suggest that activation of PKC is an important step in stimulation of endothelial cells by LPS, and that LPS and phorbol esters may synergize to produce an enhanced stimulatory effect. Our results also suggest participation of cAMP in controlling LPS-mediated stimulation of endothelial cells, but fail to demonstrate a role for protein tyrosine kinase activity.
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PMID:Signal transduction pathways of bacterial lipopolysaccharide-stimulated bovine vascular endothelial cells. 807 Sep 6

Because HIV may alter the production of inflammatory factors produced by monocytes, the expression of tumor necrosis factor alpha (TNF-alpha), tissue factor (TF), interleukin (IL)-1 beta, and IL-6 was evaluated in 47 HIV-seropositive persons and seronegative control subjects. RNA was extracted from freshly isolated lipopolysaccharide (LPS)-stimulated or unstimulated monocytes. Cytokine and TF expression was quantitated by dot blot hybridization or a reverse transcription polymerase chain reaction (RT-PCR). A significant depression of TF mRNA was observed in LPS-stimulated monocytes (66% less in AIDS, 20% less in AIDS-related complex (ARC), and 0% less in asymptomatic patients), whereas normal responses were observed for TNF-alpha, IL-1 beta, and IL-6. When constitutive expression was measured in unstimulated monocytes by RT-PCR, a differential pattern was also observed. TNF-alpha and IL-1 beta were positive in 85% of asymptomatic persons, compared with only 27% of ARC and 42% of AIDS patients. Expression of IL-6 was observed in lower proportions, 27-30%, with no significant differences among disease states. All samples were negative for TF. Thus, the regulation of inflammatory molecules is differentially altered in individuals with HIV infection. TF is preferentially down-regulated, compared with TNF-alpha, IL-1 beta, and IL-6, in LPS-stimulated monocytes as patients progress to AIDS. TNF-alpha and IL-1 beta are preferentially up-regulated, compared with IL-6 and TF, in unstimulated monocytes in asymptomatic persons, with a loss of up-regulation as patients progress to AIDS.
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PMID:Dysregulation of cytokine expression in monocytes from HIV-positive individuals. 808 6

Cemented total hip replacement surgery is associated with intraoperative cardiorespiratory depression and postoperative proximal deep vein thrombosis which may be linked to an extreme intraoperative thrombin generation and local and systemic effects of monomethylmethacrylate (MMA) released into circulation from curing cement. This in vitro study demonstrates that MMA alone or in combination with thrombin have effects on monocytes and human umbilical vein endothelial cells (HUVEC) which modulate their procoagulant activities. Moderate doses of MMA had a slight tissue factor (TF) inducing effect on monocytes. Small doses of MMA (0.1-1 mg/ml) [corrected] markedly potentiated the TF inducing effect of thrombin or lipopolysaccharide (LPS) which was included as a reference stimulant. These TF modulating effects of MMA were not seen with HUVEC. However, the generation of fibrinopeptide A (FPA) in cell overlay plasma indicated enhanced procoagulant activity of HUVEC treated with moderate doses of MMA, probably reflecting MMA cytotoxicity leading to cell retraction and exposure of extracellular matrix. Furthermore, small doses of MMA had a slight enhancing effect on FPA generation when coincubated with thrombin. These findings indicate that MMA in concentrations found in central venous blood in vivo, alone or together with thrombin, directly or indirectly exert effects that contribute to activation of coagulation.
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PMID:Effect of monomethylmethacrylate on procoagulant activities of human monocytes and umbilical vein endothelial cells in vitro. 808 39

The structural determinants of lipopolysaccharide required for the induction of tissue factor in human umbilical vein endothelial cells were studied. Intact lipid A was essential for the induction of tissue factor whereas the incomplete lipid A precursors lipid IVA and lipid X, as well as monophosphoryl lipid A and acyloxyacyl hydrolase-treated lipopolysaccharide, were unable to induce tissue factor and tissue factor specific mRNA. However, the lipid A precursor, lipid IVA, was able to inhibit LPS-mediated induction of tissue factor; structural determinants distal to lipid A were found to be required for maximal induction of tissue factor activity and tissue factor mRNA. The presence of serum in the assay was found to amplify but was not obligate for tissue factor induction by LPS.
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PMID:Induction of endothelial tissue factor by endotoxin and its precursors. 811

Microvascular thrombi underlie many of the clinical manifestations of Rocky Mountain spotted fever (RMSF), a disease characterized by Rickettsia rickettsii infection of vascular endothelial cells. Studies were designed to determine whether R rickettsii-infection of cultured human umbilical vein endothelial cells results in tissue factor (TF) induction, a process that could directly activate coagulation in infected vessels. Whereas uninfected endothelial cell cultures showed essentially undetectable TF mRNA and activity, both TF mRNA and activity were present after R rickettsii infection. TF mRNA levels were transient, peaking at 4 hours after the initiation of infection, whereas the peak of TF activity occurred at 8 hours. Induction of the TF response requires the intracellular presence of R rickettsii organisms, because uninfected rickettsia were ineffective and the response was blocked by inhibiting rickettsial entry using cytochalasin B. TF induction was not mediated by endothelial cell release of soluble factor, because no response was induced using culture medium conditioned by R rickettsii-infected cells. Furthermore, preadsorption of suspensions of R rickettsii with polymyxin B to remove contaminating lipopolysaccharide did not eliminate the TF response. Induction of TF in vital endothelial cells during R rickettsii infection could be the trigger for vascular thrombus formation of RMSF.
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PMID:Rickettsia rickettsii infection of cultured human endothelial cells induces tissue factor expression. 812 42

Cationic antibacterial proteins (CAP) were purified from rabbit granulocytes, and the effects of CAP on lipopolysaccharide (LPS)-induced tissue factor generation by murine peritoneal macrophages and human blood monocytes were studied. CAP were purified from rabbit peritoneal leukocytes by using as an assay the agglutination of erythrocytes coated with Re-LPS. Two proteins with CAP activity, CAP18 (18 kDa) and CAP7 (7 kDa), were isolated by acid extraction, ethanol precipitation, affinity chromatography, gel filtration, and reverse-phase high-pressure liquid chromatography. On the basis of protein sequencing, CAP7 was identified as the C-terminal fragment of CAP18, designated CAP18(106-142). Various forms of LPS (S-LPS, Re-LPS, and lipid A) activate murine macrophages and human blood monocytes to generate tissue factor (tissue thromboplastin). Incubation of LPS for 18 h with partially purified CAP (heparin-Sepharose fraction) inhibited the capacity of LPS to induce tissue factor; however, purified CAP18 inhibited about 75% of the activity of S-LPS after 1 h of incubation. CAP more effectively inhibited S-LPS than Re-LPS or lipid A. Synthetic CAP18(106-142) inhibited LPS-induced tissue factor generation by murine macrophages. CAP18(106-142) has greater LPS-binding and LPS-neutralizing activities than CAP18. We hypothesize that CAP18 and the derivative peptide, CAP18(106-142), bind to LPS and alter the capacity of LPS to initiate disseminated intravascular coagulation. In this regard, CAP may have therapeutic potential for sepsis and endotoxin shock.
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PMID:Characterization of a rabbit cationic protein (CAP18) with lipopolysaccharide-inhibitory activity. 813 48

Pasteurella haemolytica in cattle produces fibrino-hemorrhagic pleuropneumonia characterized by extensive pulmonary microvascular thrombosis and parenchymal necrosis. The purpose of this in vitro study was to determine if P. haemolytica lipopolysaccharide (LPS) promotes vascular thrombosis by inducing a procoagulant state in vascular endothelial cells. After treatment of confluent monolayers of bovine pulmonary artery endothelial cells with various concentrations of either P. haemolytica LPS or Escherichia coli LPS, the procoagulant activity of the endothelial cells was determined using a chromogenic assay dependent on cellular tissue factor expression. The LPS treatment induced significant increases in cellular tissue factor expression in a LPS concentration- and time-dependent manner. Highest levels of tissue factor were present at 22 hours after treatment, although high LPS concentrations induced moderate tissue factor levels at 5 hours after treatment. Interleukin-1 also induced tissue factor expression in endothelial cells and enhanced the LPS-induced effects. This interleukin-1 effect could be diminished by concurrent use of an interleukin-1 receptor antagonist. These results demonstrate that LPS and cytokine promotion of a procoagulant state in endothelial cells occurs in vitro. Similar mechanisms may play a role in P. haemolytica-mediated pulmonary vascular thrombosis.
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PMID:Tissue factor expression in bovine endothelial cells induced by Pasteurella haemolytica lipopolysaccharide and interleukin-1. 814 Jul 26

Oxidized low-density lipoprotein (oxLDL) has been characterized as an atherogenic molecule responsible for the induction of a variety of gene products. One such gene, tissue factor (TF), the cellular initiator of the coagulation cascade, is not expressed in normal vascular tissue but is expressed by monocytes and foam cells in atherosclerotic lesions. Therefore, we examined the effect of oxLDL on TF expression in cultured human adherent monocytes. Endotoxin-free oxLDL alone did not induce TF expression in adherent monocytes. However, oxLDL significantly enhanced TF expression induced by the inflammatory mediator, bacterial lipopolysaccharide (LPS), in a time- and dose-dependent manner. In contrast, oxLDL did not alter LPS-mediated production of interleukin-8 and actually inhibited LPS-induced secretion of tumor necrosis factor-alpha, suggesting that some aspects of the signaling pathways for TF induction differ from those of other LPS-responsive monocyte/macrophage gene products. Thus, this study documents specific modulation of the expression of LPS-inducible genes in monocytic cells by oxLDL. Factors that enhance TF expression in monocyte/macrophage cells present in atheroma may contribute to the severity of thrombotic episodes and complications observed in atherosclerosis.
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PMID:Oxidized LDL enhances lipopolysaccharide-induced tissue factor expression in human adherent monocytes. 817 55


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