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

Injection of bacterial lipopolysaccharide into pregnant mice resulted in fibrinogen accumulation, thrombosis and haemorrhage in the placental tissue and foetal death. Depletion of circulating fibrinogen by a thrombin-like enzyme from the venom of Malayan pit viper, Arvin, prevents foetal death. Foetal protection was also obtained by treating the mothers with a preparation of phospholipase C from Bacillus cereus known to inactivate tissue thromboplastin. It is suggested the lipopolysaccharide causes foetal death by inducing thrombosis as a consequence of activation of placental thromboplastin.
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PMID:Protection of pregnant mice with phospholipase C and with Arvin against foetal death induced by bacterial lipopolysaccharide. 44 21

Infusions of purified tissue thromboplastin in rats cause the accumulation of fibrin and platelets in the lungs and produce marked changes in the platelet count and in the coagulation factors V, VII and VIII. Tissue thromboplastin in a dose corresponding to less than 2 mug of protein per rat is lethal when given as a bolus injection. Simultaneous i.v. administration purified phospholipase C effectively prevents all these changes and protects rats from otherwise lethal doses of tissue thromboplastin. The necessary doses of phospholipase C are well below the toxic level for phospholipase C alone.
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PMID:Protection of rats by phospholipase C from Bacillus cereus against the effects of intravenous infusions of purified tissue thromboplastin. 82 58

Homogenates of several rat and human adipose tissues contain procoagulant activity mainly due to the presence of tissue thromboplastin. Intravenous injections in rats of the active fraction from such homogenates cause the accumulation of 51Cr-labelled platelets and 125I-labelled fibrin in the lungs. The effect of phospholipase C and of specific antibodies against tissue thromboplastin on this procoagulant activity of adipose tissue has been studied in vitro and in vivo.
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PMID:The procoagulant activity of adipose tissue. 91 65

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

Infusions of tissue thromboplastin induce intravascular coagulation in animals. Phospholipase C (PLC) (EC 3.1.4.3) from Bacillus cereus has a marked protective effect against such infusions and might be of value in the therapy of certain types of intravascular coagulation. We have therefore studied the toxicity, half-life, and effect on lipolysis of purified PLC in rats, using parenteral administration of 14C-labelled enzyme. Following intravenous injection, the plasma half-life was 5.2-5.4 min, and LD50 was approximately 1.6-1.7 mg/kg. The effect of PLC on lipolysis was moderate. The enzyme does not appear to be bound to any plasma macromolecules, and there was no accumulation of labelled enzyme in tissues other than kidney.
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PMID:Parenteral administration of phospholipase C in the rat. Distribution, elimination, and lethal doses. 100 44

alpha-Toxin, the major cytolysin of Staphylococcus aureus, promotes blood coagulation by its attack on human platelets (Bhakdi S., Muhly, M., Mannhardt, U., Hugo, F., Klapettek, K., Mueller-Eckhardt, C., and Roka, L. (1988) J. Exp. Med. 168, 527-542). In the present study we demonstrate that toxin attack on gel-filtered human platelets initiates the assembly of prothrombinase complexes at rates up to 10-fold of controls. Treatment of platelets with 0.1 microgram/ml alpha-toxin resulted in generation of 1.4 units of thrombin/10(8) platelets. A similar rate of thrombin generation was noted when platelets were subjected to three cycles of freezing and thawing. However, the alpha-toxin-induced prothrombinase activity was not due to platelet lysis, since less than 1% of total cellular lactate dehydrogenase was released by this alpha-toxin concentration. Two distinct and dissociable processes contributed to enhanced prothrombinase assembly. First, alpha-toxin promoted the exocytotic release of factor V from alpha-granules, which was accompanied by co-secretion of platelet factor 4. This process was calcium-dependent. Second, toxin-treated platelets exhibited an enhanced capacity to bind external factor V(a), a phenomenon that was not linked to Ca2(+)-dependent factor V secretion. Assembly of prothrombinase complexes via these two mechanisms together accounts for the procoagulant action of S. aureus alpha-toxin.
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PMID:Staphylococcus aureus alpha-toxin attack on human platelets promotes assembly of the prothrombinase complex. 211 11

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

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

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

This report describes studies on the activation of coagulation factor VII (FVII) and the inhibition of the extrinsic coagulation pathway in acute ischaemic heart disease. FVII and the inhibitor of the tissue thromboplastin-FVII complex, called extrinsic pathway inhibitor (EPI), were determined in plasma from 68 patients and compared to findings in 37 normal individuals. The mean FVII amidolytic activity, the mean FVII clotting activity, as well as the FVII clotting/FVII amidolytic ratio were not significantly different in the patient groups as compared to the controls. The fraction of FVII clotting activity that is sensitive to phospholipase C, 'the FVII-phospholipid complex', was 8% in controls, 19% (P less than 0.05) in patients with acute myocardial infarction, 15% (n.s.) in angina pectoris and 13% (n.s.) in heart failure/arrhythmia patients. The 'FVII-phospholipid complex' was highly significantly correlated to triglycerides in plasma in patients with acute myocardial infarction (r = 0.88, P less than 0.001) and angina pectoris (r = 0.89, P less than 0.001). The mean EPI levels were significantly increased in patients with acute myocardial infarction (132%), angina pectoris (134%), and heart failure (150%) as compared to the control population (110%). The FVII clotting/EPI ratio was significantly decreased both in patients with acute myocardial infarction and heart failure, whereas the FVII amidolytic/EPI ratio was significantly decreased only in the heart failure group. Apparently, in patients with acute ischaemic heart disease, a moderate increase in the procoagulant activity is accompanied by a marked increase in the anticoagulant activity of the extrinsic coagulation pathway, suggesting a balanced activation system.
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PMID:Factor VII and extrinsic pathway inhibitor in acute coronary disease. 278 54


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