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)

Monocytes are able to specifically bind heparin rapidly, reversibly, and saturably with 5.5 +/- 2.6 x 10(6) binding sites per monocyte and a dissociation constant of 330 +/- 221 nmol/l. Moreover, at least 40-50% of the cell-bound heparin can be internalized. Heparin binding by monocytes is affected by cell stimulation with an increase of the availability of binding sites after challenge with calcium ionophore, lipopolysaccharide, and interleukin 2. The interaction of heparin with monocytes reversibly decreases the expression of tissue factor on the cellular surface, so hampering the cellular procoagulant potential.
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PMID:Heparin, monocytes, and procoagulant activity. 196 69

Interleukin-1 (IL-1) plays a major role in inflammatory responses. Activation of coagulation and fibrin deposition typical of these reactions is mediated by macrophage procoagulants induced on stimulated macrophages. IL-1 activity in the supernatant of lipopolysaccharide (LPS)-stimulated guinea-pig macrophages was markedly enhanced by the presence of thrombin during macrophage activation. Although thrombin alone had no effect, inclusion of 1 mU/ml of thrombin with suboptimal levels of LPS produced a 200-fold increase in IL-1 activity, and further enhancement was observed with increasing doses of thrombin. The active site of thrombin was necessary for enhancement, as the serine esterase inhibitor di-isopropyl-fluorophosphate (DIP) and hirudin inhibited the synergy observed with LPS and thrombin. Prothrombin and Factor Xa also enhanced IL-1 production, although not to the same extent as thrombin. Factor Xa-like activity was demonstrated on the surface of LPS-stimulated macrophages. Both the Xa-like activity and IL-1 generated by LPS-stimulated cells were inhibited by heparin. Heparin with a high affinity for antithrombin III (anti-coagulant heparin; HAH) inhibited IL-1 generation, whereas low-affinity heparin (non-anticoagulant; LAH) had no effect. We show that proteases of the extrinsic coagulation cascade enhance IL-1 generation and propose that a Factor Xa-like activity present in activated macrophages, together with thrombin, may be important in IL-1 processing.
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PMID:Thrombin and factor Xa enhance the production of interleukin-1. 222 24

The fibrinolytic potency of several polyanions was comparatively investigated. Fibrinolytic activity was measured in a whole plasma assay using H-D-Val-Leu-Lys-pNA (S-2251) as chromogenic substrate and by a fibrin plate assay using plasminogen rich fibrin plates. In the chromogenic substrate assay potent fibrinolytic polyanions comprised dextran sulfate, GAGPS, pentosan polysulfate, polyanethol sulfate, l-carrageenan and i-carrageenan. Chondroitin sulfates A, B, C, keratan sulfate, ribonucleic acid, k-carrageenan and heparin were weakly fibrinolytic. Hyaluronic acid and lipopolysaccharide from E. coli were inactive. Similar results were obtained when fibrinolytic activity was measured by a fibrin plate assay. All polyanions except lipopolysaccharide produced lysis zones. Induction of fibrinolytic activity in human plasma was shown to be at least partially dependent on Hageman factor. In factor XII deficient plasma no fibrinolysis was induced by any of the polyanions when measured in the fibrin plate assay. In the chromogenic substrate assay corn Hageman factor inhibitor (CHFI) inhibited the activation of S-2251 cleaving enzyme by GAGPS, pentosan polysulfate, polyanethol sulfate, heparin, and ribonucleic acid near completely. The activation by dextran sulfate was inhibited by 45%. Heparin, pentosan polysulfate and GAGPS, three polyanions of therapeutic interest were separately compared. In both assays GAGPS proved the most potent activator, while pentosan polysulfate exhibited 83% and 44% and heparin 32% and 14% of GAGPS fibrinolytic activity in the chromogenic substrate test and the fibrin plate assay, respectively.
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PMID:Induction of fibrinolysis by polyanions in human plasma. 246 1

The mechanisms of tumor cytotoxicity of rat polymorphonuclear leukocytes (PMN) activated with cytokine(s) were studied with the use of supernatants from a rat myelomonocytic leukemia cell line, WRT-7, incubated in the presence of bacterial lipopolysaccharide (LPS) (LPS WRT-7 sup) as a source of cytokine. Rat peritoneal PMN treated with LPS WRT-7 sup showed cytostasis from 3 hr after the start of incubation, while significant cytolysis was first observed after 24 hr. When target tumor cells were separated from PMN at 6 or 12 hr after the start of the assay, 3H-UdR release from the separated target cells comparable to that from the group incubated with PMN for the whole assay time of 40 hr was observed during the following incubation, which indicates that priming for subsequent lysis occurs at a relatively early stage of the assay. None of various scavengers of active oxygens, inhibitors of heme enzymes, and inhibitors of neutral proteinases inhibited cytolysis mediated by PMN stimulated with LPS WRT-7 sup. Heparin inhibited PMN cytolysis only when it was added within 1 hr after the start of the assay. Fractionation of heparin by ion exchange chromatography showed a parallelism between the negative charge and the inhibitory effect of heparin on PMN cytotoxicity.
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PMID:The mechanisms of cytotoxicity to tumor cells by polymorphonuclear leukocytes stimulated with cytokines. 313 Dec 85

The optimal conditions for performance of a sensitive functional assay for the human alternative complement pathway were studied. The serum dilution causing 50% lysis of rabbit erythrocytes in magnesium EGTA buffer is designated the APH50 titer. Optimal reaction conditions for the assay were pH 7.2, incubation temperature 37 degrees C, incubation time 60 minutes, and magnesium concentration 0.002 M. Lowering the ionic strength of the buffer from 0.150 M to 0.0125 M increased APH50 titers nearly 2.5-fold, but decreased the reproducibility of titers. Significant fluid-phase conversion of C3 at 37 degrees C in low ionic strength buffer was demonstrated by crossed immunoelectrophoresis. Using the optimal reaction conditions, in normal ionic strength buffer the mean APH50 +/- SD for 45 normal adults was 25.3 +/- 5.7 U/mL. Heparin, an inhibitor of the alternative pathway, decreased APH50 by 50% at a concentration of 100 U heparin/mL serum, and totally abolished alternative pathway hemolytic activity at 1,000 U heparin/mL serum, while lowering CH50 titers to a much lesser degree. When increasing doses of zymosan were used for complement activation in vitro, the per cent APH50 depletion at low doses of zymosan was at least twice the per cent depletion of CH50 or antigenic P, B, and C3. A striking dichotomy between nearly complete APH50 depletion and normal or near normal CH50 and hemolytic C4 levels was documented for a human burn patient and for a baboon infused with a lethal dose of Escherichia coli lipopolysaccharide. Therefore, we documented a substantially greater sensitivity of APH50 than of conventional complement determinations for detecting complement consumption by alternative pathway activators.
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PMID:A study of optimal reaction conditions for an assay of the human alternative complement pathway. 684 95

The effects of early immunization with DNA and of injection of bacterial lipopolysaccharide (LPS) on the glomerulonephritis of NZB x NZW mice were studied. Combined injections of DNA complexed to methylated bovine serum albumin (DNA-mBSA) and of LPS appeared to be more efficient in accelerating the disease in NZB x NZW mice than injections of DNA-mBSA or LPS alone. A rapid increase in levels of anti-DNA antibodies, an early appearance of severe renal lesions and a shortened survival were observed in mice injected with both DNA-mBSA and LPS. This new model was found to be suitable for therapeutic studies in mice with accelerated disease treated with cyclophosphamide and heparin. The efficacy of cyclophosphamide for the treatment of NZB x NZW mouse disease was shown by immunological and histological studies in mice younger than 4 months. Heparin appeared to have a beneficial effect by preventing the endocapillary cellular proliferation induced by injections of DNA-mBSA and LPS. The accelerated model of NZB x NZW mouse disease might be a useful tool for experiments on the treatment of lupus nephritis.
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PMID:Acceleration of glomerulonephritis in NZB x NZW mice by early immunization with DNA and injection of bacterial lipopolysaccharide. Experimental approach to the treatment of lupus nephritis by use of the accelerated model of NZB x NZW mouse disease. 744 9

Release of previously incorporated 45Ca from fetal rat bone in tissue culture was stimulated by preparations of the polymorphonuclear leukocyte chemotactic factor isolated from lipopolysaccharide (LPS)-induced inflammatory exudate in rabbits as well as by Bacteroides fragilis LPS. High concentrations of released hydroxyproline and lactate seemed to correlate well as a high percentage of 45Ca liberated into the culture medium. An active bone resorption was stimulated by a concentration of 1 microgram/ml of the chemotactic factor. The peak in amount of released 45Ca was at a concentration of 5 micrograms/ml of the chemotactic factor (LPS-CF) as well as of the LPS preparation, whereas the parathyroid hormone was most active at 1 IU/ml. Their effect was connected with the formation of osteoclasts. Neither LPS-CF nor LPS stimulated a release of 45Ca or hydroxyproline from heat-devitalized bones. Heparin added to LPS-CF did not enhance its resorptive potential, whereas when added to LPS it had a synergistic effect. It is suggested that the bone resorptive effect exerted by LPS may be caused by chemotactic factors elaborated by activation of the complement system, and that these factors may be of importance in the pathophysiology of periodontal disease.
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PMID:Effects of a chemotactic factor and Bacteroides fragilis lipopolysaccharide on bone resorption in tissue culture. 744 24

Plasminogen activator inhibitor-1 (PAI-1) is a primary endogenous inhibitor of tissue-type plasminogen activator (t-PA). In this study, we examined the effects of oversulfated fucoidan (OSF) derivatives and heparin on lipopolysaccharide (LPS)-induced release of PAI-1 antigen from cultured human umbilical vein endothelial cells (HUVEC). Addition of LPS (10 micrograms/ml) enhanced the release of PAI-1 by HUVEC but not of t-PA antigen. At 18 h, a 2.4-fold increase in the extracellular PAI-1 level was observed. The increased PAI-1 level was reduced to control level by the simultaneous addition of 10 micrograms/ml of OSF or heparin. The suppressive effect of native fucoidan was negligible. We also examined the molecular size effect of OSF, using 10-20, 20-40, and 40-60 kDa fragments. The result indicated that these fragments were effective as well as the 100-130 kDa form of OSF, hence suggesting an important role of the degree of sulfation. Interleukin-1 beta (IL-1 beta) is a potent inducer of PAI-1 in cultured HUVEC. Heparin, OSF, and its fragments did not suppress the IL-1 beta-induced release of PAI-1 antigen. Treatment of HUVEC with heparitinase or monoclonal antibody against heparin sulfate proteoglycan (HSPG) resulted in a complete loss of its ability to enhance PAI-1 release in response to LPS stimulation, while the chondroitinase ABC treatment hardly affected the PAI-1 production. These results suggest that HSPG is involved in the initial binding of LPS to HUVEC. The suppressive effects of OSF and heparin on LPS-induced PAI-1 release may result from the inhibition of LPS binding to the cell surface HSPG.
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PMID:Oversulfated fucoidan and heparin suppress endotoxin induction of plasminogen activator inhibitor-1 in cultured human endothelial cells: their possible mechanism of action. 757 76

We investigated the effect of activated protein C (APC) on lipopolysaccharide (LPS)-induced pulmonary vascular injury in rats to investigate the possible usefulness of APC as a treatment for adult respiratory distress syndrome. Intravenously administered LPS (5 mg/kg) significantly increased pulmonary vascular permeability. APC prevented the LPS-induced increase in pulmonary vascular permeability observed at 6 hours. Heparin plus antithrombin III (ATIII) and active site-blocked factor Xa (DEGR-Xa), a selective inhibitor of thrombin generation, inhibited LPS-induced coagulopathy but did not prevent LPS-induced pulmonary vascular injury. LPS-induced pulmonary vascular injury was significantly attenuated in rats with nitrogen mustard-induced leukocytopenia and in rats treated with ONO-5046, a potent granulocyte elastase inhibitor. Administration of LPS also increased pulmonary accumulation of leukocytes, as evaluated by measurement of myeloperoxidase activity in the lungs. APC significantly reduced LPS-induced increases in pulmonary accumulation of leukocytes at 1 hour. Neither ATIII plus heparin nor DEGR-Xa inhibited leukocyte accumulation. Active site-blocked APC (DIP-APC) prevented neither the LPS-induced pulmonary accumulation of leukocytes nor the LPS-induced increase in pulmonary vascular permeability. These results suggest that the mechanism of APC inhibition of LPS-induced pulmonary vascular injury was independent of its anticoagulant activity and was related to its ability to inhibit accumulation of leukocytes. In addition, these findings suggest that the serine protease activity of APC may be essential to its inhibitory effect on LPS-induced pulmonary accumulation of leukocytes and subsequent pulmonary vascular injury.
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PMID:Activated protein C attenuates endotoxin-induced pulmonary vascular injury by inhibiting activated leukocytes in rats. 855 86

Stimulated monocytes are involved in blood clotting and fibrin dissolution by synthesizing tissue factor (TF) and fibrinolytic components such as plasminogen activator inhibitor type 2 (PAI-2). Heparin interacts with smooth muscle cells, platelets, and endothelial cells and specifically binds to human monocytes. In endothelial and smooth muscle cells, heparin selectively inhibits collagenase and tissue plasminogen activator gene expression. To investigate (1) heparin's influence on the hemostatic system by its interactions with plasma factors and cellular elements and (2) to determine its effects on gene expression in blood circulating cells, we studied the effect of heparin on TF and PAI-2 protein and mRNA in human lipopolysaccharide (LPS)- or interferon-gamma (IFN-gamma)-stimulated monocytes. TF and PAI-2 proteins were investigated by ELISA and by assaying procoagulant activity. The mRNA study was carried out by an initial PCR screening followed by a Northern blot semiquantitative analysis. Heparin (0.5 U/mL) inhibited both TF and PAI-2 production and gene expression. The contemporaneous protein and mRNA decrease (TF and PAI-2 protein 22 and 42%, respectively; suggests that this action is, at least partially, at the transcriptional level. The effect is not specific for heparin and is not demonstrated by other glycosaminoglycans (chondroitin-4-sulfate or dermatan sulfate). This action may be relevant for the antithrombotic activity of heparin in cell-mediated blood clotting activation.
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PMID:Tissue factor and plasminogen activator inhibitor type 2 expression in human stimulated monocytes is inhibited by heparin. 920 Mar 37


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