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)

Coagulation disorders have been associated with the use of chemotherapeutic drugs. Pharmacological doses of cisplatin and adriamycin directly induced low levels of procoagulant on normal human blood monocytes and on a human myelomonocytic cell line, RC2a. Activity was maximal after 24 h and was not due to cell lysis as increasing drug doses which decreased cell viability were less effective. Procoagulant induction was markedly enhanced in the presence of bacterial lipopolysaccharide (LPS), with as little as 10-100 pg/ml LPS potentiating the cisplatin response by 2-5-fold and more than doubling the adriamycin response. Greater than 90% of the procoagulant activity was membrane-bound tissue factor as indicated by the factor VII-dependent generation of factor Xa by viable cells and by the neutralization of this activity by a monoclonal antibody to tissue factor. Tissue factor antigen was measured simultaneously by immunohistochemical staining and by cell ELISA. Blood monocytes activated with LPS expressed high levels of tissue factor antigen; by contrast, adriamycin and cisplatin did not appear to induce antigen expression, but to enhance the specific activity of that already present. Results suggest that membrane alterations which occur following treatment with DNA/RNA intercalating drugs, may result in a highly active form of monocyte/macrophage tissue factor which may contribute to the complications caused by activated coagulation. Secondary Gram-negative infection or cytokines released by an active immune response to a tumour may contribute to the procoagulant potential of these cytotoxic drugs.
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PMID:Modulation of tissue factor on human monocytes by cisplatin and adriamycin. 139 Feb 32

We established a method for measuring procoagulant action on human umbilical vein endothelial cells (HUVEC). HUVEC (2.5 x 10(4)/well) were stimulated with 1 microgram/ml endotoxin (lipopolysaccharide: LPS) for 6 hours at 37 degrees C in 5% CO2. After washing, the HUVEC were incubated with assay buffer containing Proplex ST 1 unit (factor VII)/ml, S2222 0.6 mg/ml and CaCl2 6.6 mM, for 30 minutes at 37 degrees C. The procoagulant activity was determined by measuring the supernatant at OD405. Calphobindin I, II and III (CPB I, CPB II and CPB III) are the calcium dependent phospholipid binding proteins that exhibit anticoagulant activity in vitro. In this study, we investigated the effects of CPB I, CPB II and CPB III on procoagulant activity (PCA) expressed on HUVEC. The results are as follows 1) CPBI inhibits the procoagulant activity on HUVEC in a dose-dependent manner (IC 50% less than 0.4 microM). The same doses (0.4 microM) of CPBII and CPBIII decreased the procoagulant activity to 28.1% (CPBII), and to 84.6% (CPB III). CPB anticoagulant activities were, CPBII greater than CPBI greater than CPBIII, in that order. 2) When 0.05% H2O2 was added to the cell culture medium wells, concentrations of CPBI in supernatants increased in a time-dependent manner, and they reached to the maximum after 8 hours. CPBI in supernatants after 24 hours were not detected without H2O2, but concentrations of 4.88 ng/ml/10(4) cells with 0.01% H2O2, and 9.60 ng/ml/10(4) cells with 0.05% H2O2 were detected.
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PMID:[Effect of coagulation inhibitor proteins (Calphobindins) on tissue factor expression of endothelial cells]. 145 41

The procoagulant activity (PCA) of disrupted monocytes was examined in 32 diabetic patients (26 with insulin-dependent and 6 with non-insulin-dependent diabetes) versus 30 control subjects. Diabetes monocytes exhibited a weak PCA before any incubation, associated in 10 cases with a significant amount of factor VII activity. Incubation led to a significant rise in PCA in diabetes cells, when stimulated with lipopolysaccharide or not, and in control cells only after stimulation. In incubated diabetes cells, PCA was prothrombinase-like when factor VII was associated with the freshly isolated cells, and tissue factor-like (as in the controls) when no factor VII was associated with the cells. The characteristics of PCA were not correlated with clinical features or with the type of diabetes. Our study suggests that diabetes monocytes exhibit a higher level of PCA than control ones, possibly corresponding to an in vivo stimulation, or at least a higher responsiveness to stimuli occurring in vitro.
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PMID:Distinctive features of procoagulant response of monocytes from diabetic patients. 273 77

We have studied concurrent production of macrophage agglutination factor (MAggF) and procoagulant activity by antigen-stimulated human blood mononuclear cells to gain insight into biochemical mechanisms underlying delayed hypersensitivity inflammatory reactions. After stimulation of cells from tuberculin-sensitive donors with tuberculin, MAggF was present in culture supernatants while the overwhelming majority of procoagulant activity remained cell-associated. Neither MAggF nor procoagulant activity was found in reconstituted control cultures, nor in tuberculin-stimulated cultures of non-sensitive cells. Concanavalin A and lipopolysaccharide elicited both activities from cultured mononuclear cells, regardless of donor sensitivity. Human MAggF bound to insolubilized gelatin, heparin and a monoclonal anti-fibronectin (FN) antibody, and its activity was inhibited by another monoclonal antibody directed against the gelatin-binding domain of FN. Treatment of indicator peritoneal exudate cells with monoclonal anti-FN receptor antibody inhibited their response to human MAggF. These results suggest that human MAggF, like the analogous guinea-pig activity, is FN-associated. Antigen-elicited procoagulant activity shortened the recalcification time of normal, factor VII- and factor IX-deficient plasma, partially corrected prothrombin times of factor VII-deficient plasma, had no effect on recalcification and prothrombin items of factor X- and factor V-deficient plasma, and was inhibited by specific anti-factor VII antibody. Thus, human mononuclear cell procoagulant consists of both tissue factor and factor VII, whether it is induced by antigen or mitogen. Antigen-stimulated blood mononuclear cells are able to provide a signal for local fibrin deposition and a protein mediating fibrin binding to mononuclear phagocytes and collagen at sites of delayed hypersensitivity reactions.
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PMID:Concurrent production of macrophage agglutination factor and factor VII by antigen-stimulated human peripheral blood mononuclear cells. 293 89

Monkey (Macaca fuscata) mononuclear leukocytes were stimulated to produce thromboplastin (tissue factor) upon exposure to lipopolysaccharide, LPS. The stimulation was dose-related in the concentration range of 10(-5) to 10(-1) micrograms/ml of LPS. Lipid A portion of the LPS molecule was essential to induce the leukocyte ability for tissue factor generation. Thus, a lipid-lipid interaction between LPS and the cells is a plausible trigger for eliciting the ability. Approximately 50% of the tissue factor thus produced appeared to be located on the cell surface, at which the coagulation cascade is probably initiated via the activation of factor VII. Among monkey mononuclear cell populations, monocytes were responsible for LPS-induced tissue factor production. Lymphocytes amplified the basal ability of monocytes to produce the factor by two-fold at physiological lymphocyte-monocyte ratios of 8:1 to 10:1. This indicates a complementary effect of lymphocytes upon the LPS-mediated monocyte ability. The medium supernatant from LPS-stimulated lymphocytes affected the monocyte competence while the stimulated lymphocytes did not. This result suggests that a soluble product of lymphocytes, i.e., lymphokine-like mediator, but not the cellular entity, participates in LPS-induced tissue factor production of monocytes.
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PMID:Monocyte thromboplastin (tissue factor): complementary effect of lymphocytes upon its generation by endotoxin-stimulated monkey (Macaca fuscata) cells. 403 Jul 40

Mononuclear phagocytes, stimulated by bacterial lipopolysaccharide (LPS), have been implicated in the activation of coagulation in sepsis and endotoxemia. In monocytes LPS induces the synthesis of tissue factor (TF) which, assembled with factor VII, initiates the blood coagulation cascades. In this study we investigated the mechanism of LPS recognition by monocytes, and the consequent expression of TF mRNA and TF activity. We also studied the inhibition of these effects of LPS by rBPI23, a 23-kD recombinant fragment of bactericidal/permeability increasing protein, which has been shown to antagonize LPS in vitro and in vivo. Human peripheral blood mononuclear cells, or monocytes isolated by adherence, were stimulated with Escherichia coli O113 LPS at physiologically relevant concentrations (> or = 10 pg/mL). The effect of LPS was dependent on the presence of the serum protein LBP (lipopolysaccharide-binding protein), as shown by the potentiating effect of human recombinant LBP or serum. Furthermore, recognition of low amounts of LPS by monocytes was also dependent on CD14 receptors, because monoclonal antibodies against CD14 greatly reduced the LPS sensitivity of monocytes in the presence of serum or rLBP. Induction of TF activity and mRNA expression by LPS were inhibited by rBPI23. The expression of tumor necrosis factor showed qualitatively similar changes. Considering the involvement of LPS-induced TF in the potentially lethal intravascular coagulation in sepsis, inhibition of TF induction by rBPI23 may be of therapeutic benefit.
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PMID:Monocyte tissue factor induction by lipopolysaccharide (LPS): dependence on LPS-binding protein and CD14, and inhibition by a recombinant fragment of bactericidal/permeability-increasing protein. 751 3

Measles virus infection of microvascular endothelium in vivo and ensuing endothelial cell activation may be important in the pathogenesis of subsequent inflammation in target organs. This study investigated the capacity of measles virus to induce procoagulant activity, in vitro, in endothelial cells isolated from human umbilical cord veins. Endothelial cells were infected with a clinical isolate of measles virus propagated in Vero cells. Cells were also incubated with bacterial lipopolysaccharide (10 micrograms/ml), herpes simplex virus type 1, cytomegalovirus or culture medium alone as positive and negative controls, respectively. Endothelial cell procoagulant activity was measured in a one-stage clotting assay. Measles virus stimulated both a time and dose-dependent endothelial cell procoagulant response by the induction of tissue factor synthesis, confirmed by both immunocytochemistry and its dependence on factor VII for activity. This activity was reduced by u.v.-irradiation of the virus. Infected cells were analysed by double immunofluorescent staining for both tissue factor and measles virus N-protein, and examined using confocal scanning laser microscopy. Cells expressing tissue factor were also positive for the measles virus N-protein. Low levels of interleukin-1 were detected in some viral inocula derived from measles virus-infected Vero cells, however neutralising antibody to interleukin-1 failed to inhibit the endothelial cell procoagulant response to measles virus, whereas it significantly reduced procoagulant activity induced in endothelial cells by recombinant interleukin-1. The capacity of measles virus to induce endothelial tissue factor in vitro, may be relevant to the thrombotic vasculopathy associated with measles virus infection in vivo.
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PMID:Measles virus induction of human endothelial cell tissue factor procoagulant activity in vitro. 796 98

The tissue factor activity in blood monocytes was investigated during ovarian stimulation for in-vitro fertilization (IVF) in 13 women. Blood samples were taken prior to hormonal stimulation (days 2-3 of the menstrual cycle, median serum oestradiol concentration 70 pmol/l) and the day after ovulation induction with human chorionic gonadotrophin (days 11-13, median serum oestradiol concentration 6270 pmol/l). The tissue factor activity in unstimulated monocytes and factor VII concentration were unchanged during the treatment. However, the tissue factor activity in lipopolysaccharide-stimulated monocytes was on average more than twice as high after stimulation (P < 0.02). A positive correlation was found between the tissue factor activity and the serum concentration of oestradiol (r = 0.514, P < 0.02). The tumour necrosis factor (TNF)-alpha increased during ovarian stimulation (P = 0.05), and there was a positive correlation between the change in TNF-alpha and the change in tissue factor activity (r = 0.663, P < 0.05). Our results indicate an enhanced sensitivity of the extrinsic coagulation system during IVF treatment since more tissue factor is available upon stimulation. It is suggested that this may be important in thrombotic situations. Further studies are necessary to elucidate the mechanism behind this response.
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PMID:Enhanced sensitivity of the extrinsic coagulation system during ovarian stimulation for in-vitro fertilization. 825 16

Tissue factor, the cellular receptor for factor VII/VIIa, activates both the intrinsic and extrinsic pathways of blood coagulation. In this analysis we have used DNase I footprinting to map the sites of protein-DNA interaction along the promoter (-383 to +8) using nuclear extracts prepared from uninduced and lipopolysaccharide-induced THP-1 cells. We have identified six regions that interact with nuclear factors in both uninduced and induced extracts. Four footprints are contained within a region reported to confer base-line high level expression and lipopolysaccharide and serum induction. Two additional footprints map to a region reported to reduce basal transcription by 50%. The only qualitative change in the footprint pattern with uninduced and induced extracts is the appearance of two hypersensitive sites with uninduced extracts. In addition, changes in the level of protein- DNA binding are detected with only one probe by DNA mobility shift analysis. A combination of well characterized transcription factors (AP1), primarily lymphoid cell specific regulatory proteins (NF-kappa B- and/or Ets-1-related proteins), as well as additional, uncharacterized proteins appear to interact with these sequences. Our data suggest that post-translational modification of existing transcription factors, and not induction of new DNA-binding activity, mediates the lipopolysaccharide induction of tissue factor synthesis in THP-1 cells.
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PMID:Lipopolysaccharide induction of tissue factor expression in THP-1 monocytic cells. Protein-DNA interactions with the promoter. 828 2

Tissue factor (TF), a small membrane bound high affinity receptor for factor VII, has an important procoagulant role in the haemostatic dysfunction associated with severe sepsis. Using an in vitro model of human endothelial TF expression, defined strains of Neisseria meningitidis were found to upregulate endothelial cell procoagulant activity (PCA) in a dose dependent manner. This TF response was detected with as little as 10(4) cfu/ml and reached similar levels to those seen with high concentrations of purified endotoxin (> 1 ng/ml). Treatment of N. meningitidis with either adult donor immune serum, penicillin or gentamicin failed to enhance this PCA. Limulus amoebocyte lysate assay of lipopolysaccharide in bacterial culture filtrates together with polymyxin B inhibition experiments suggest that endotoxin is largely responsible for endothelial TF induction by N. meningitidis. Incubation of endothelial cells with N. meningitidis B1940 and B1940 siaD- (an eight-fold more adherent unencapsulated isogenic strain), revealed a significantly greater TF response to B1940 siaD- (P < 0.01). In conclusion, bacterial adhesion to the vessel wall and therefore local levels of endotoxin may be important determinants of the endothelial procoagulant response to N. meningitidis and the consequent coagulopathy commonly associated with the disease.
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PMID:Induction of human endothelial tissue factor expression by Neisseria meningitidis: the influence of bacterial killing and adherence to the endothelium. 916 Feb 96


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