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 plasma level of interleukin-1 beta (IL-1 beta) was determined in normal individuals, patients with disseminated intravascular coagulation (DIC), patients in the pre-DIC period (within 7 days before the onset of DIC), and non-DIC patients to examine the relationship between DIC and the plasma IL-1 beta level. The plasma IL-1 beta level was 0-0.085 ng/ml in normal individuals, with little difference being seen according to related age. It was significantly higher in the DIC group (0.19 +/- 0.19 ng/ml) than in the pre-DIC group (0.05 +/- 0.08 ng/ml) or the non-DIC group (0.09 +/- 0.01 ng/ml). The plasma IL-1 beta level was not markedly elevated in leukemia patients, even in the DIC group, but it was significantly increased in the DIC group of solid cancer patients and was generally elevated in patients with sepsis. It was markedly elevated to 0.39 +/- 0.26 ng/ml in patients with organ failure. When mononuclear cells were incubated with lipopolysaccharide, it was found that IL-1 beta, tumor necrosis factor, and tissue factor (TF) were released into the medium, and there was an increase of TF release from endothelial cells incubated with this medium. These results suggest that the increase in IL-1 beta reflected the activation of monocytes and may be an important factor in DIC and its associated organ failure.
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PMID:Plasma level of IL-1 beta in disseminated intravascular coagulation. 205 18

The induction of pulmonary alveolar macrophage (PAM) tissue factor-dependent procoagulant activity is central to the deposition of inflammatory fibrin in the pulmonary alveolus. The presence of enhanced tissue factor activity is often associated with pulmonary fibrin deposition, an important pathogenetic event that can delay resolution of pulmonary inflammation and promote the induction of pulmonary fibrosis. Since tissue factor synthesis induction and activation pathways are potential therapeutic targets for modulation of alveolar macrophage tissue factor (procoagulant) activity, we examined the pathways through which endotoxin lipopolysaccharide (LPS) induces bovine PAM tissue factor-dependent procoagulant activity. PAM procoagulant activity was markedly enhanced to 10 times the levels of freshly isolated PAM after 8 h of culture in the presence of either the protein kinase C (PKC) agonist phorbol 12-myristate 13-acetate (PMA) or LPS. Both LPS-(P less than 0.002) and PMA-induced activity (P less than 0.007) was completely ablated by the PKC inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H 7,100 microM) but was unaffected by the cyclic nucleotide-dependent protein kinase inhibitor N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004, 100 microM). The arachidonate cyclooxygenase pathway inhibitor phenylbutazone (10(-4) M) had modest effects that were not statistically significant. The unstimulated increase of procoagulant activity in 8-h cultures was unaffected by the same inhibitory modulations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endotoxin-mediated bovine alveolar macrophage procoagulant induction is dependent on protein kinase C activation. 209 May 87

Cisplatin, doxorubicin and daunorubicin (drugs which intercalate with DNA) influenced the membrane-bound procoagulant potential of murine thioglycollate-induced peritoneal exudate (TG-PEC) macrophages and the monocytoid cell line WEHI 265, whereas the antimetabolites 5-fluorouracil and methotrexate had no effect. Enhanced procoagulant was not caused by non-specific toxicity of these agents. Cisplatin directly increased the procoagulant expressed on WEHI 265 cells, whereas MPCA on TG-PEC was enhanced only when cisplatin was combined with a second stimulant, either bacterial lipopolysaccharide (LPS) or interferon (IFN gamma). WEHI 265 cells failed to respond to the anthracycline drugs, either alone or in combination with LPS, whereas they enhanced the IFN gamma response. Doxorubicin and daunorubicin increased the LPS response of TG-PEC by approximately 4-fold and the IFN gamma response by approximately 10-fold. Pulsing experiments suggested that the anthracyclines enhanced procoagulant expression by a mechanism different from cisplatin. Daunorubicin primed TG-PEC within 4 hr to respond to low levels of LPS, whereas either LPS or cisplatin primed these cells to respond to cisplatin or LPS respectively. Furthermore, the procoagulant expressed by TG-PEC stimulated by LPS/cisplatin had properties of tissue factor (TF: 50% total activity) and Factor VIIa (50% total procoagulant)-like activities, whereas the predominant procoagulant on LPS/anthracycline activated TG-PEC was TF-like (70% total activity) with weak Factor VIIa and prothrombinase-like properties.
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PMID:Induction of macrophage procoagulant expression by cisplatin, daunorubicin and doxorubicin. 212 Jan 34

Plasma levels of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) and the in vitro ability of platelets to aggregate and of monocytes to express procoagulant (tissue factor) activity (PCA) were evaluated in five patients who are homozygous for familial hypercholesterolemia (FH) before and after a single and a regular 5-month cholesterol removal by low density lipoprotein (LDL) apheresis. The biweekly procedure resulted in a 25% to 30% reduction (approximately 150 mg/dl) in total and LDL cholesterol (both were greater than 550 mg/dl at the beginning of the study). The basal levels of t-PA antigen and fibrinolytic activity before and after 10 minutes of venous stasis, basal PAI activity, and PAI-1 antigen were comparable to controls and were not affected by LDL apheresis. Likewise, regardless of the cholesterol removal, the PCA of freshly isolated monocytes and that of monocytes incubated with lipopolysaccharide did not differ from control values. Finally, the pre-apheresis sensitivity of platelets to adenosine diphosphate, arachidonic acid, and collagen was 1.5 to 2 times the normal value. This ratio was unchanged throughout the 5-month procedure. We conclude that fibrinolysis and monocyte PCA are normal in FH patients, whereas platelet aggregation is abnormally high, and none of these parameters is significantly affected by a 25% to 30% reduction in total and LDL cholesterol by LDL apheresis. Furthermore, our data suggest that removal of cholesterol from plasma by LDL apheresis is important for gaining insight into the mechanisms involved in the ischemic complications of arteriosclerosis in FH patients.
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PMID:Hemostatic variables in homozygous familial hypercholesterolemia. Effect of regular plasma cholesterol removal by low density lipoprotein apheresis. 212 91

Macrophages, unlike CD4+ T cells, can be productively infected by human immunodeficiency virus (HIV) without prior cellular activation. Cytopathic infection ensues without the induction of tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), or tissue factor genes. In detailed studies on TNF alpha, HIV infection did not affect the regulation of TNF alpha in response to bacterial lipopolysaccharide. In an effort to examine the interferon responsiveness of HIV-infected macrophages, the cells were challenged with vesicular stomatitis virus (VSV) with or without interferon pretreatment. Surprisingly, HIV-infected macrophages were completely resistant to VSV-induced lysis even in the absence of interferon; however, no interferon was detected in the supernatants of these infected cells. The resistance of HIV-infected macrophages to superinfection with VSV indicates a previously undescribed effect of HIV upon macrophage cellular metabolism.
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PMID:Characterization of a macrophage-tropic HIV strain that does not alter macrophage cytokine production yet protects macrophages from superinfection by vesicular stomatitis virus. 217 98

Monocytes can be induced to synthesize and express tissue factor procoagulant activity. They can also be stimulated to release a broad spectrum of inflammatory agents including superoxide anion (O2-) that are thought to contribute to the pathogenesis of inflammatory diseases. Dipyridamole, an inhibitor of platelet aggregation blocks the lipopolysaccharide (LPS)-induced increase in monocyte-associated tissue factor activity and phorbol myristate acetate (PMA) stimulated O2- release from monocytes and polymorphonuclear leukocytes (PMN). Dipyridamole inhibition of O2- release can be reversed by increased glucose in the culture media, whereas dipyridamole inhibition of tissue factor can not be reversed by increased glucose in the culture media. These results reveal that dipyridamole influences monocytes by at least two distinct mechanisms. Further, it may serve as an anti-thrombotic agent by virtue of its effect on both platelet aggregation and monocyte tissue factor activity.
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PMID:Dipyridamole inhibits O2- release and expression of tissue factor activity by peripheral blood monocytes stimulated with lipopolysaccharide. 217 22

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

Whereas tissue factor (TF), a 47 kDa transmembrane glycoprotein, is constitutively present in certain tissues such as epithelial tissue, brain, and placenta, it is normally not expressed by cells within the vasculature. However, inflammatory mediators including bacterial lipopolysaccharide (LPS) can stimulate the expression of cell surface procoagulant activity (PCA) on monocytes. In our present study the kinetics (over 24 h) of molecular TF expression on LPS-stimulated monocytes analyzed by flow cytometry corresponds closely to functional PCA of human mononuclear blood cells (MBC). Both PCA and TF expression on monocytes were rapid events reaching their maximum after about 6 h of stimulation. At this time approximately 70-80% of monocytes had also achieved maximum anti-TF MAb receptor density. For certain analytical applications, monitoring of molecular TF expression on monocytes by flow cytometry using anti-TF MAb is favorable because there is no influence by PCA inhibitors.
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PMID:Flow cytometric analysis of tissue factor (TF) expression on stimulated monocytes--comparison to procoagulant activity of mononuclear blood cells. 229 87

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

Fibrin formation plays an important role in glomerular injury. We therefore examined the procoagulant signal produced by cultured rat mesangial cells. Actively growing mesangial cells produced procoagulant activity (PCA) that was present in intact cells (surface-associated), was inhibitable by cyclohexamide and which, by clotting assay, had the characteristics of tissue factor. This PCA decreased with incubation of cells in serum-deprived medium. Incubation with bacterial lipopolysaccharide (LPS) and tumor necrosis factor (TNF alpha) induced increased detectable tissue factor by mesangial cells within two hours which was maximal by four hours. We conclude that quiescent mesangial cells produce a small amount of tissue factor-like procoagulant activity, and that this PCA can be stimulated by incubation with TNF alpha, LPS or when cells are actively growing in high serum medium. Therefore mesangial cells have the capability of contributing to fibrin formation during inflammatory glomerular injury or sepsis.
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PMID:Tissue factor production by cultured rat mesangial cells. Stimulation by TNF alpha and lipopolysaccharide. 234 26


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