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

Human vascular endothelium plays a major role in hemostatic processes. Human venous endothelial cells (HEC) may promote coagulation by generation of thromboplastin. This tissue factor production is enhanced by bacterial lipopolysaccharide (LPS). However, the mechanisms of this enhancement remain unclear. In order to quantify by image analysis the nuclear modifications induced by LPS on HEC, umbilical cord vein HEC were cultured in vitro with or without E. coli LPS (10 micrograms/ml) for 0 to 6 h. At the end of culture, tissue factor expression was evaluated by the ability of a cellular extract to shorten the coagulation time of human citrated plasma. Simultaneously, the morphology of LPS treated and control HEC was analysed using a SAMBA 200 cell image processor after Feulgen staining. This analysis indicates that LPS treatment induces nuclear modifications as early as 1 h after culture onset, before any tissue factor expression. This activity appears only between 2 and 4 h of culture with LPS. Our data show that image analysis permits the detection of very early nuclear events in HEC and that these events precede the expression of functional properties which may be implicated in thrombotic processes.
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PMID:Nuclear textural changes preceding endotoxin mediated enhancement of thromboplastin synthesis in human endothelial cells in vitro. 227 59

Expression of tumor necrosis factor (TNF alpha), tissue factor (TF), and interleukin 1-beta (IL-1 beta) mRNA was evaluated in monocytes isolated from patients infected with human immunodeficiency virus (HIV). There was a significant depression (66%) of the induced level of TF mRNA expression in response to lipopolysaccharide. Conversely, the response of TNF alpha and IL-1 beta, following LPS induction, was "normal." TF mRNA reduction was also observed to a lesser degree in AIDS-related complex patients (20%) but not in asymptomatic seropositives. TF is necessary for initiation of the coagulation protease cascade, leading to thrombin production and fibrin deposition, which play a role in inflammatory responses. Its selective reduction may be a factor in the diminished resistance to secondary infections observed in AIDS. Further, since the TF defect increases as patients progress toward AIDS, it may serve as a marker for disease progression.
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PMID:A selective defect in tissue factor mRNA expression in monocytes from AIDS patients. 229 2

The results of a study conducted to determine the clinico-pathological changes in 4 experimentally-induced cases of endotoxaemia in the horse are reported on. Endotoxaemia was induced by injecting commercially available E. coli 055:B5 lipopolysaccharide intravenously at a dose of 1 microgram kg-1. The haematocrit, red cell count, total and differential white cell counts, thrombocyte count, prothrombin time, partial thromboplastin time, fibrinogen level, level of fibrin degradation products, arterial acid-base status, serum lactate and blood glucose were determined repeatedly. Changes that occurred, include increases in the haematocrit and red cell count, a leucopaenia followed by a leucocytosis caused mainly by changes in the number of neutrophils, the development of disseminated intravascular coagulation, minor changes in the arterial acid base parameters, hyperglycaemia followed by hypoglycaemia and an increase in serum lactate.
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PMID:[Clinico-pathological changes after intravenous administration of endotoxin in the horse]. 248 30

Although thrombosis is a frequent complication of total parenteral nutrition (TPN), its pathogenesis has received little scientific attention. We have studied, in vitro, the effects of the component solutions of TPN on the induction and modulation of human monocyte procoagulant activity, an initiator of coagulation. Human peripheral blood mononuclear cells were cultured with (a) 200 microliters of dextrose solution (10%, 15%, 20%, 25%, and 50%), (b) 200 microliters of amino acid solution (full, one-half, and one-quarter strength), and (c) 200 microliters of isosmolar 10% lipid emulsion (LE). Cocultures of LE and 20% dextrose, LE and full-strength amino acid solution, and LE and bacterial lipopolysaccharide were also studied. Cells cultured with lipopolysaccharide or medium alone constituted positive and negative controls, respectively. In addition, cocultures of LE and 20% dextrose, LE and full-strength amino acid solution, and LE and lipopolysaccharide were also studied. Cells were incubated for intervals of 12-72 h, washed, frozen, and assayed for monocyte procoagulant activity (MPCA). Milliunits of MPCA were derived from a standard thromboplastin curve. In addition, spontaneous MPCA levels were measured in healthy volunteers (n = 4) and "home" total parenteral nutrition patients (n = 4) before and after a 2-h infusion of 500 ml of LE. Our results show that, in vitro, hypertonic dextrose and full-strength amino acid solutions induce significant levels of MPCA. Induction of MPCA by dextrose was lymphocyte-independent. Although a significant increase in MPCA by full-strength amino acid solution was seen in cultures of isolated monocytes, a lymphocyte requirement was demonstrated for full MPCA. In contrast, LE significantly inhibited the induction of MPCA by 20% dextrose and full-strength amino acid solution. This inhibitory activity was at the monocyte level. Subfractionation of the LE into triglyceride and phospholipid phases showed the inhibitory capacity to reside in the former. In vivo, patients on home total parenteral nutrition expressed higher spontaneous MPCA levels than normal controls. Ten percent lipid emulsion infusion abolished MPCA expression in both groups. These corroborative in vitro and in vivo data suggest a mechanism for the thrombogenicity of total parenteral nutrition solutions and that the inhibitory properties of LE may be of practical advantage in preventing thrombosis.
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PMID:Thrombogenicity of total parenteral nutrition solutions: I. Effect on induction of monocyte/macrophage procoagulant activity. 250 84

Thrombosis is a common sequela of total parenteral nutrition. We have recently demonstrated in vitro that hypertonic total parenteral nutrition solutions are potent inducers of a tissue factor monocyte procoagulant activity, the initiating cofactor of the extrinsic clotting cascade. We have further studied, in vitro, the effects of the component solutions of total parenteral nutrition on the induction and modulation of endothelial cell procoagulant activity. Cultured porcine aortic endothelial cells were incubated with (a) 200 microliters of dextrose solution (5%, 10%, 20%, 25%, and 50%), (b) 200 microliters of amino acid solution [full strength (N), one-fourth strength, and one-half strength], and (c) 200 microliters of 10% lipid emulsion. Cocultures of lipid emulsion and 20% dextrose, lipid emulsion and full-strength 10% amino acid solution (N-amino acid), and lipid emulsion and bacterial lipopolysaccharide also were studied. Cells were incubated for intervals of 3-108 h, washed and frozen, harvested, and assayed for endothelial cell procoagulant activity. Units of endothelial cell procoagulant activity were derived from a standard thromboplastin curve. Our results show that amino acid and hypertonic dextrose total parenteral nutrition solutions are able to strongly induce endothelial cell procoagulant activity expression in vitro. In contrast, lipid emulsion significantly inhibited the induction of endothelial cell procoagulant activity by 20% dextrose, N-amino acid, and lipopolysaccharide. These results provide further evidence for the role of the cellular pathways of coagulation in total parenteral nutrition-induced thrombosis. Furthermore, the inhibitory properties of lipid emulsion may be of practical advantage in reducing total parenteral nut induced thrombosis.
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PMID:Thrombogenicity of total parenteral nutrition solutions: II. Effect on induction of endothelial cell procoagulant activity. 250 85

We have evaluated the quantitative relationship between lipopolysaccharide (LPS, endotoxin), fibrinopeptide A (FPA), antithrombin (AT), protein C (PC) and extrinsic pathway inhibitor (EPI) in plasma from 39 consecutively admitted patients with systemic meningococcal disease (SMD). The most severely ill patients with fulminant meningococcal septicemia (n = 13, 6 dead) had significantly (p less than 0.01) higher plasma levels of LPS and FPA and lower levels of PC and AT on admission as compared with the less severe clinical presentations (n = 26, 1 dead). The levels of EPI on admission were significantly (p less than 0.05) higher in nonsurvivors vs survivors with fulminant septicemia. As the disease progressed, the levels of LPS, FPA, AT and PC declined, while the levels of EPI increased. Three of six nonsurviving septicemic patients had levels of EPI greater than 200% within 16 hours of admission vs two of 30 survivors (p = 0.02). The results suggest that increasing levels of LPS in SMD elicit increasing consumption coagulopathy, contributing to the organ pathophysiology. The kinetics of EPI, inhibiting the thromboplastin-FVIIa-FXa complex, differs markedly from the kinetics of AT and PC i.e. increases as opposed to decreases.
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PMID:The quantitative association of plasma endotoxin, antithrombin, protein C, extrinsic pathway inhibitor and fibrinopeptide A in systemic meningococcal disease. 251 Mar 54

Tissue factor is a lipoprotein, expressed on the surface of cells, which binds coagulation Factor VII or VIIa, leading to activation of Factors X and IX with subsequent fibrin generation. Cellular tissue factor activity is important in pathophysiologic processes such as inflammation and disseminated intravascular coagulation. In this study, the long-chain base sphingosine inhibited coagulation initiated by lipopolysaccharide-stimulated intact human monocytes. Sphingosine (5-100 microM) also profoundly inhibited thromboplastin-initiated coagulation (greater than 90% decrease in thromboplastin activity). This inhibition was dose- and time-dependent. Sphingosine inhibited neither the intrinsic pathway of coagulation nor thrombin generation of fibrin. The sphingosine analogues sphingomyelin, ceramide, or N-acetylsphingosine did not affect thromboplastin activity, suggesting that the polar head of sphingosine was necessary for interaction of the molecule with the coagulation system. Investigation of the biochemical mechanism revealed that sphingosine (5-50 microM), but neither sphingomyelin nor ceramide, inhibited specific binding of radiolabeled Factor VII to lipopolysaccharide-stimulated intact monocytes. The results suggest that sphingosine may regulate monocyte tissue factor-initiated coagulation by modulating Factor VII binding to tissue factor. Sphingosine may represent a new class of inhibitors of hemostasis.
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PMID:Sphingosine inhibits monocyte tissue factor-initiated coagulation by altering factor VII binding. 280 83

A remarkable variation in monocyte activation among individuals was observed when blood from different people was incubated with lipopolysaccharides. To elucidate this phenomenon, we studied intracellular signals associated with monocyte activation. This was done by measuring induced thromboplastin synthesis. An inhibitor of phospholipase A2 blocked the lipopolysaccharide induced synthesis of thromboplastin. Thus, release of arachidonic acid (20: 4) seemed to be necessary to activate the monocytes. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, had no effect on the monocyte activation in subjects with a low response to lipopolysaccharides (low responders); this contrasted with nearly 80% inhibition in individuals with very sensitive cells (high responders). Taking aspirin raised monocyte activation by an average of 50%, this was caused by the effect of aspirin on the platelets. Platelets enhanced the lipopolysaccharide activation of monocytes 2-3 fold. The high response phenomenon was partially due to platelets. When platelets in the blood of high responders were substituted with platelets from low responders, the monocyte activation fell by up to 70%. Fatty acids seemed to play a central role in the activation of monocytes. Intake of cod liver resulted in significant reduction of induced thromboplastin synthesis. It is suggested that those who are high responders may be more susceptible to developing atherosclerosis.
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PMID:Fatty acids, platelets and monocytes. Something to do with atherogenesis. 292 3

Recombinant gamma-interferon (r gamma-IFN) has contrasting effects on thromboplastin (TPL) synthesis induced in monocytes (M) and endothelial cells by bacterial lipopolysaccharide (LPS), phorbol ester (TPA), and phytohaemagglutinin (PHA). In human umbilical vein endothelial cells (HUVEC) the induced thromboplastin response was significantly augmented by r gamma-IFN whereas the monocyte response was inhibited. Recombinant alpha-interferon (r alpha-IFN) had no effect on thromboplastin induction in endothelial cells but had a significant inhibitory effect on the TPL response in monocytes when LPS or LPS and cyclosporin A (CS) were used as inducing agents. Cyclosporin A, previously shown to enhance thromboplastin synthesis induced in monocytes, also contributes to a higher level of thromboplastin activity in endothelial cells. Its effect on monocytes was in most cases fully inhibited by r gamma-IFN (and also by r alpha-IFN when tested). gamma-Interferon and alpha-interferon alone had a weak stimulatory effect or none on thromboplastin synthesis in both cell types.
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PMID:Differential effect of alpha-interferon and gamma-interferon on thromboplastin response in monocytes and endothelial cells. 312 8

The human myelomonocytic cell line RC2a expressed procoagulant activity following stimulation with human lymphokine (LK) prepared by stimulating peripheral blood mononuclear cells with either mitogens (Concanavalin A, phytohaemagglutinin or antigen (tuberculin). Induction was rapid, with optimal activity observed between 6 and 8 h, was decreased in cultures containing serum and was not inhibited by actinomycin D or cycloheximide. The LK activity was not inhibited by an anti-interferon gamma (IFN gamma) antibody. IFN gamma and phorbol myristate acetate (PMA) had no activity but acted in synergy to induce procoagulant expression; interferon alpha plus PMA were without effect. In contrast to the LK-induced response, procoagulant induced by IFN gamma/PMA was not detected for up to 8 h and steadily rose over 24-48 h culture and was dependent on new protein and RNA synthesis. Bacterial lipopolysaccharide, a potent inducer of thromboplastin on normal human monocytes, failed, either alone or in combination with LK, IFN gamma, PMA or IFN gamma plus PMA, to activate procoagulant expression on RC2a cells. Both LK and IFN gamma/PMA-induced procoagulant had properties of thromboplastin expressed both intracellularly and on intact, viable cells. This study shows that RC2a cells are responsive to factors produced as the result of an activated cell-mediated immune response which may therefore contribute to the coagulopathies common to this form of malignancy.
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PMID:Procoagulant induction by human lymphokine and interferon gamma/PMA on a myelomonocytic cell line, RC2a. 314 14


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