Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of several kinds of carbohydrate oxidase, SH-inhibitors and some other chemical reagents on the activities of von Willebrand factor, factor VIII procoagulant and factor VIII-related antigen were studied. Factor VIII procoagulant and von Willebrand factor activities were both inhibited by galactose oxidase, p-hydroxymercuribenzoic acid, 2,4,6-trinitrobenzensulfonic acid and sodium periodate, alpha-Mannosidase, N-ethylmaleimide and phospholipase C inactivated factor VIII procoagulant but not von Willebrand factor activity. Dithiothreitol had little effect on factor VIII procoagulant activity but reduced significantly that of von Willebrand factor. It is suggested that galactose and the thiol and epsilon-aminogroup groups of lysine may play an important role in both factor VIII procoagulant and von Willebrand factor activity. Mannose may be responsible for the factor VIII procoagulant activity but not for the von Willebrand factor activity. The Laurell rocket heights of factor VIII-related antigen rose with increasing concentration of galactose oxidase, 2,4,6-trinitrobenzenesulfonic acid or sodium periodate. Gel filtration experiments showed that factor VIII-related antigen may be dissociated into subunits by galactose oxidase but not by 2,4,6-trinitrobenzenesulfonic acid or sodium periodate.
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PMID:Studies of von Willebrand factor: effects of different kinds of carbohydrate oxidases, SH-inhibitors and some other chemical reagents. 30 2

Although pulmonary fibrin deposition and coagulation abnormalities have been observed in acute lung injury in humans, their role in the pathogenesis of pulmonary disorders is unclear. In order to gain further insights into the role of the coagulation in lung injury, we examined the relationship between procoagulant activity in bronchoalveolar lavage (BAL) fluids and the evolution of bleomycin-induced lung injury in marmosets. The BAL procoagulant activity was increased at 1, 2, and 4 wk after bleomycin challenge compared with that in control subjects, and it was capable of shortening the recalcification times of plasmas deficient in factor VII and factor VIII but not in factor X. This profile suggested the presence in BAL of an activator of factor X. Activation of purified human factor X by BAL was demonstrated by measuring the amidolytic activity of the generated factor Xa on its N-benzoyl-L-isoleucyl L-glutamyl-glycyl-L-argenine-p-nitroanilide substrate. Factor X activating activity was increased in BAL at 2 wk after bleomycin challenge. Cleavage of 125I-labeled human factor X by BAL from bleomycin-challenged marmosets yielded a 55,500 Mr product that comigrated with factor Xa, the appearance of which correlated strongly with amidolytic evidence of factor Xa activity. Electron microscopy of the lungs of animals from all groups revealed pulmonary fibrin deposition at 2 wk after bleomycin challenge, at the time of increased BAL procoagulant and factor X activating activity. The BAL procoagulant activity was completely sedimentable by ultracentrifugation and was inhibited by concanavalin A and phospholipase C. Activation of purified factor X by BAL was inhibited by monospecific polyclonal goat and rabbit antibodies to human factor VII as well as antibody to bovine tissue factor, demonstrating that factor X activating activity in BAL was attributable to tissue factor associated with material similar to factors VII or VIIa. We conclude that procoagulant activity in BAL increases after bleomycin challenge in marmosets and is attributable to activation of factor X by tissue factor associated with factors VII or VIIa-like material. Increased BAL procoagulant activity is temporally associated with pulmonary fibrin deposition and pulmonary fibrosis during bleomycin-induced pulmonary injury in the marmoset.
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PMID:Bronchoalveolar lavage procoagulant activity in bleomycin-induced lung injury in marmosets. Characterization and relationship to fibrin deposition and fibrosis. 244 Mar 56

Washed human platelets were incubated with commercial factor VIII concentrate, or with purified factor VIII coagulant moiety. Platelets were then washed again and lysed by sonication. VIII:Ag and vWf:Ag were measured in the platelet lysate prior to and after incubation of the lysate with phospholipase C (PL-C). Platelet bound VIII:Ag was significantly higher after incubation of washed platelets with factor VIII concentrate than after incubation with buffer. Platelet bound VIII:Ag was further increased when platelets had been incubated with concentrate in the presence of thrombin and collagen. In contrast, only a slight increase in platelet bound vWf:Ag was observed after incubation of platelets with concentrate. When washed platelets had been incubated with factor VIII coagulant moiety, also significantly more platelet bound VIII:Ag was observed than after incubation with buffer. Measurable VIII:Ag, but not vWf:Ag, increased significantly after incubation of the platelet lysate with PL-C. When intact washed platelets had been treated with PL-C prior to the incubation with concentrate, binding of VIII:Ag to platelets was nearly completely abolished. Our data suggest that the factor VIII coagulant moiety binds to phospholipids of the platelet membrane and thereby contributes to the assembly of the factor X activating complex on the platelet surface.
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PMID:Factor VIII coagulant moiety binds to platelets by binding to phospholipids of the platelet membrane. 310 60

Cell-free supernatants (sol phases), obtained after centrifugation (50,000 x g for 45 minutes) of respiratory tract secretions from horses with chronic pulmonary disease, were assayed for procoagulant activity (PCA) in a one-stage clotting assay. Of the 103 specimens tested, 59% (61) contained PCA. Procoagulant activity was detected most often in respiratory tract secretions of severely affected horses and was correlated with the quantity of neutrophils in the respiratory tract secretions. In 12 of the 17 secretions tested, the clotting time was decreased in a dose-dependent manner. However, in the coagulation assay, some reversal of PCA or inhibition of coagulation was observed in 4 secretion specimens when greater volumes of sol phase were added. Procoagulant activity was characterized tentatively as tissue factor, because it was temperature stable and was inhibited by phospholipase C and by concanavalin A. Clotting was induced in factor VIII-deficient human plasma; however, with the exception of 1 respiratory secretion specimen, clotting was not enhanced in factor VII-deficient human plasma. Procoagulant activity is a useful indicator of airway inflammation.
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PMID:Procoagulant activity in respiratory tract secretions from horses with chronic pulmonary disease. 339 15

Disseminated intravascular coagulation invariably accompanies placement of peritoneovenous (LeVeen) shunts, which suggests that ascitic fluid contains procoagulant material capable of activating blood coagulation. In this study, we identified thrombogenic activity in human ascites and the hemostatic pathway by which it acts. Peritoneal fluid was removed percutaneously from patients with ascites due to various causes. Four fractions were prepared by centrifugation: cells, a low-speed, cell-free fluid, a high-speed supernatant, and the precipitate from the high-speed centrifugation. Cellular fractions from all ascitic fluids shortened a one-stage clotting time of normal pooled plasma by 68% in comparison with saline solution and endotoxin controls. Similarly, the cell-free fluids also shortened the clotting time of normal pooled plasma by 41%. The cellular and cell-free fractions shortened the clotting time of factor VIII-deficient plasma but failed to demonstrate procoagulant activity in factor VII-deficient plasma. These fractions had no effect on platelet aggregation or the platelet release reaction. The high-speed precipitate was dissociated by ethylenediaminetetra-acetate (EDTA) into fluid phase and precipitate, both of which demonstrated procoagulant activity. Furthermore, high-speed precipitate contained protein, phospholipid, and sterol in proportions similar to those of plasma membranes and contained membrane-bound vesicles as identified by means of electron microscopy. This material could be rendered inactive by heating to 100 degrees C for 2 minutes or by incubation with phospholipase C for 15 minutes. Finally, the ability of the high-speed precipitate to shorten the clotting time was prevented by preincubation with a monoclonal antibody, which is known to inhibit the procoagulant activity of human tissue factor. We suggest that several entities contribute to the procoagulant properties of human ascites, with procoagulant material deriving at least in part from peritoneal cells. The sedimentable procoagulant factor appears to be associated with cellular membranes or membrane fragments and is thromboplastin-like in its chemical composition, immunoreactivity, and substrate specificity.
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PMID:Preliminary characterization of the procoagulant material in human ascites. 358 68

Various n-formylated peptides function as receptor-specific chemoattractants for both granulocytes and monocytes. Because these agents are important tools in the study of leukocyte function in vitro, we chose to examine their effects on leukocyte procoagulant activity. The synthetic chemotactic peptide N-formyl-methionyl-leucyl phenylalanine (FMLP) induces a fourfold increase in procoagulant activity (PCA) in cultured human monocytes at an optimal dose of 5 X 10(-9) mol/L, whereas higher doses inhibit PCA response. Although nonadherent lymphocytes are not absolutely required for PCA expression, their presence significantly amplifies monocyte PCA. Irradiation of nonadherent lymphocytes before mixing them with FMLP and adherent cells abolishes their ability to amplify PCA. Kinetic studies demonstrate an increase in optimal dose FMLP-stimulated PCA over time whereas high-dose inhibition of PCA generation occurs at various incubation times. Cell viability is unaffected by inhibitory concentrations of FMLP. Supernates from high-dose FMLP-stimulated cells fail to inhibit later expression of PCA by cells exposed to endotoxin. The cellular procoagulant remains cell-bound and exhibits characteristics of thromboplastin (tissue factor), including inhibition by concanavalin A and phospholipase C as well as the ability to shorten the clotting times of factor VIII but not factor VII-deficient substrate plasmas. These results suggest a complex system of lymphoid cell regulation of procoagulant generation by monocytes exposed to various chemotactic peptides in vitro.
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PMID:Regulation of monocyte procoagulant by chemoattractants. 397 Oct 40

Human peripheral blood leucocytes were examined for their ability to synthesize procoagulant activity in tissue culture. A method was developed utilizing silica coated with polyvinylpyrrolidone (Percoll) to separate monocytes from lymphocytes prior to culture. Coagulation activity was demonstrated in all mononuclear cell cultures after 24 hours incubation. This activity was inhibited by phospholipase C which suggested that tissue thromboplastin was the major source of activity. Specific immunoradiometric assays failed to demonstrate synthesis of factor VIII related antigen (FVIIIRAG) or factor VIII coagulant antigen. The results indicate that under conditions of this study factor VIII was not synthesized in mononuclear cell cultures.
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PMID:Characterization of procoagulant activity produced by cultures of human monocytes and lymphocytes separated in colloidal silica-polvinylpyrrolidone gradients. 615 91

The recovery and initial half-disappearance rate of factor VIII procoagulant activity (VIIIC) and procoagulant antigen (VIIICAg) were studied in 9 haemophilia A patients following infusion of factor VIII concentrates to varying plasma VIIIC levels. While VIIIC recovery was independent of dose, the VIIICAg recovery varied in a dose-dependent fashion. The excess of VIIICAg relative to VIIIC found in the factor VIII concentrates (VIIICAg/VIIIC ratios of 1.9-3.1) was not observed in plasma samples taken after low level infusions (plasma VIIIC less than 1 U/ml) but a significant excess of VIIICAg was observed in higher level infusions. The VIIICAg recovery of post-infusion plasma was not increased by treatment with phospholipase C.
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PMID:Factor VIII procoagulant antigen recovery is a dose-related response to Factor VIII concentrate infusions. 643 42