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)

As a background for the development and testing of phospholipase C in the therapy of post-traumatic and post-surgical intravascular coagulation, highly purified tissue thromboplastin was injected i.v. into rats. The levels of factor V, VII, VIII and blood platelets and the activity of the intrinsic coagulation pathway in general (the cephalin test) were followed. Histological examination of pulmonary, kidney and liver tissue was carried. The dose-response was highly dependent on the injection rate. A marked activation of factor VII and a fall in the activities of factors V and VIII as well as in thrombocyte counts were observed. Very few or no thrombi were seen beyond the pulmonary circulation. The main changes (fibrin-containing thrombi and platelet aggregates) were observed in the lungs during the first 15 min after injection. Atter 15 min virtually no thrombi or platelet aggregates could be detected. The effect of tissue thromboplastin was counteracted by large doses of antithrombin III.
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PMID:The effect of intravenous injection of purified human tissue thromboplastin in rats. 93 13

Twenty patients accepted for coronary bypass surgery were randomized to receive either a concentrated ethylester compound of n-3 fatty acids, with a daily dose of 3.15 g of eicosapentaenoic acid (EPA) and 1.89 g of docosahexaenoic acid (DHA), or corn oil (controls) in a double blind study, to evaluate the effect on lipids, platelets and coagulation during the pre- and postoperative phase. Only patients with fasting triglyceride (TG) levels greater than or equal to 1.6 mmol/l at recruitment were eligible. The study was continued for 5 to 6 months. Surgery was usually performed at mid-intervention. Blood samples were collected during morning hours in fasting subjects, just prior to intervention, preoperatively and at final postoperative follow-up. Moreover, blood loss was accurately accounted for postoperatively. A threefold increase (p = 0.0001) of EPA was noted at pre- and postoperative follow-up. TG-levels were reduced 20 and 39%, respectively, in patients on n-3 fatty acids, reaching statistical significance at end of intervention (p = 0.034). TG-levels in controls remained largely unchanged. In patients on n-3 fatty acids, there was a statistically significant increase in serum total cholesterol preoperatively, but this change was no longer present at completion of the study. No significant changes were noted in platelet function, as judged by bleeding time, collagen induced platelet aggregation and release of TxB2 during aggregation. Parameters of extrinsic coagulation, including phospholipase C-sensitive factor VII (PLC-VII) and extrinsic pathway inhibitor (EPI), also remained essentially unchanged in both groups of patients. However, fibrinogen was significantly reduced in controls (p less than 0.05) at end of intervention.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of a concentrated ethylester compound of n-3 fatty acids on lipids, platelets and coagulation in patients undergoing coronary bypass surgery. 177 12

The reduction of plasma factor VII (FVII) activity by phospholipase C (PLC), in vitro, has been proposed as a possible indication of a risk of cardiovascular disease. The ability of PLC to reduce FVII activity was found to require calcium ions and the presence of triglyceride-rich lipoproteins (e.g. chylomicra and very-low density lipoproteins) rather than high or low density lipoproteins. The PLC-mediated reduction of FVII activity was prevented by pre-incubation of PLC with chylomicra, before adding FVII, and this suggests that PLC may act on triglyceride-rich lipoproteins already bound to FVII in order to reduce FVII activity. At optimal PLC concentration, the extent of the reduction in FVII activity was proportional to the concentration of chylomicra. The detergent, Tween, prevented any loss of FVII activity, in both plasma and purified systems, if it was present at the beginning of the incubation with PLC. Addition of Tween, but not EDTA, after inhibition of FVII activity had occurred, caused a partial restoration of FVII activity. It is concluded that PLC reduces FVII activity by modifying triglyceride-rich lipoproteins to a form which binds to FVII, independently of calcium ions, and which inhibits procoagulant activity. The detection of PLC-sensitive procoagulant activity. The detection of PLC-sensitive FVII activity may therefore have no greater significance than the measurement of plasma triglyceride levels in predicting a risk of cardiovascular disease.
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PMID:Phospholipase C mediated inhibition of factor VII requires triglyceride-rich lipoproteins. 186 15

Factor X-activating activity (FXAA) was determined by a chromogenic assay in normal and malignant breast tissue. FXAA was found in all tissue (n = 38) irrespective of pathology, and the activity of normal tissue was similar to that of tumours. FXAA correlated with tissue hemoglobin in normal breast (p less than 0.02) but not in tumours. FXAA was markedly reduced by aluminium hydroxide, barium citrate, anti-human factor VII, DFP, PMSF and phospholipase C, but was unaffected by iodoacetamide and mercuric chloride. It is concluded that FXAA is a serine protease with the properties of a tissue factor-factor VII complex. FXAA occurs in normal and malignant breast tissue, although the 'normal' activity may be an artefact of the homogenization process.
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PMID:Factor X-activating procoagulant in normal and malignant breast tissue. 228 55

Fibrin deposition in the alveolar space and the lung interstitium is a prominent feature of many types of inflammatory pulmonary diseases. Cells of the monocyte/macrophage line are the primary cells supplying procoagulant activity in inflammatory lesions. In the present study we found that both lung alveolar macrophages (LAM) and bronchoalveolar lavage fluids (BALF) from humans contained procoagulant activities. The procoagulant in BALF was associated with membrane vesicles which sedimented at 100,000 g for 1 h. By electron microscopy the BALF ultrasediment was seen to consist almost exclusively of membrane material and this was confirmed by monitoring the content of different marker enzymes for specific subcellular structures. Using macrophage membrane markers, at least part of the BALF-ultrasediment was shown to be derived from LAM. On the basis of phospholipase C sensitivity, antibody neutralization and the site of action of the procoagulant in the sequential activation of coagulation factors, both the LAM-associated and the BALF-associated procoagulant activity was identified as thromboplastin (tissue factor) or thromboplastin-factor VII complexes. This suggests that alveolar macrophages and the LAM-derived thromboplastin-containing microvesicles may contribute to intraalveolar and interstitial fibrin deposition in vivo and probably also have consequences for the development of pulmonary fibrosis.
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PMID:Procoagulant (thromboplastin) activity in human bronchoalveolar lavage fluids is derived from alveolar macrophages. 231 34

We have previously reported the existence of a phospholipase C-sensitive form of factor VII-probably a factor VII-phospholipid complex in normal pregnancy. By bivariate regression analysis, the level of this complex shows highly significant positive correlations with serum triglycerides (r = 0.90, p less than 0.0001) and blood platelet count (r = 0.067, p = 0.0004). This high degree of correlation was verified by stepwise multiple regression analysis. It is presently not known how this factor VII complex formes.
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PMID:Phospholipase C-sensitive factor VIII activity in normal pregnancy. 238 12

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

The proposed link between a circulating factor VII-phospholipid complex and the risk of cardiovascular disease (CVD) has stimulated us to investigate the effect of phospholipase C (PLC) on the factor VII (FVII) activity in plasma from healthy individuals. PLC caused a rapid fall in FVII activity which was larger with heparinized than with citrated plasma. EDTA inhibited the PLC effect so emphasizing the involvement of divalent cations. PLC dependent loss of FVII activity varied widely between individuals, showed a highly significant correlation with plasma triglyceride concentrations, and was always greater in post-prandial compared to fasting plasma samples. Experiments using pure recombinant FVIIa and plasma depleted of FVII by adsorption indicated that loss of FVII activity only occurred in the simultaneous presence of absorbed plasma, FVIIa and PLC. Preincubation of PLC with adsorbed plasma before adding FVIIa did not lead to loss of FVII activity. It appears that PLC may act on lipoproteins already bound to FVII, in order to inhibit FVII activity. Other results indicated that competition between different plasma components (lipoproteins) in binding to FVII may govern the extent of the PLC dependent reduction in FVII activity.
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PMID:The effect of phospholipase C on plasma factor VII. 251 68

In cultured human monocytes/macrophages, surface expression of procoagulatory activity (PCA) was induced by chemically modified LDL (acetyl-LDL and MDA-LDL) in a dose- and time-dependent manner. Maximum PCA (30-fold increase) was detected after 24 h of culture with modified LDL at doses of 25-750 micrograms protein/ml. Using factor VII deficient human plasma and phospholipase C this PCA was identified as tissue thromboplastin activity (factor III). These results suggest a further atherogenic potential for modified LDL through stimulation of the conversion of fibrinogen to fibrin in the atheromatous lesion.
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PMID:Enhanced procoagulatory activity (PCA) of human monocytes/macrophages after in vitro stimulation with chemically modified LDL. 278 95

An increase in factor VII coagulant activity (FVIIc) was found in patients with high thrombotic risk and in hyperlipidemias, namely in Fredrickson's types IIb and IV. This elevation was correlated with the level of total cholesterol and triglyceride concentrations. It has been suggested that this increase is due to higher FVII coagulant activity related to the formation of a complex between factor VII (FVII) and phospholipids, since it was shown that FVIIc returns to normal levels after incubation of plasma with phospholipase C. In this respect we have studied the activity of FVII before and after phospholipase C plasma treatment and FVII related antigen (FVIIag) in patients with types IIa, IIb and IV hyperlipidemias. An elevation of FVIIc was found in hyperlipidemic patients compared to normal controls. FVIIag values were also higher in type IV patients, implicating an increase in FVII total concentration and not only an activation of FVII. Furthermore, Phospholipase C action on patients' plasma samples lowered FVIIc to levels very similar to those of FVIIag. In normal controls the same action was noted and it seems therefore likely that the proposed phospholipid contribution to FVIIc hyperactivity plays only a minor role in FVII changes in primary hyperlipidemia. Instead, FVIIag increase seems to be the major mechanism of FVII increase in primary hypertriglyceridemic patients.
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PMID:Phospholipase C sensitive FVII activity and FVII antigen in hypertriglyceridemia. 291 18


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