Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human monocytes in vitro respond to various agents (immune complexes, lectins, endotoxin, the divalent ionophore A 23187, 12-O-tetradecanoyl-phorbol 13-acetate [TPA], purified protein derivative [PPD] of Bacille Calmette-Guerin) with an increased synthesis of the protein component of thromboplastin. The effect of cyclic AMP and cyclic GMP on this response has been studied. Dibutyryl-cyclic AMP, prostaglandin E1 and the phosphodiesterase inhibitors 3-butyl-1-methyl-xanthine (MIX) and rac-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 20-1724), separately and in combination have a pronounced inhibitory effect on the response to immune complexes and PPD, and a moderate effect on the response to endotoxin and lectins. The effect on TPA response and on the response to A 23187 was slight. Dibutyryl-cyclic GMP (1 mM) gave a slight inhibition of the TPA and IC response, but had essentially no effect on the response to other inducers. The intracellular cAMP level increased when monocytes were incubated with IC, TPA or A 23187 followed by a decrease to basal levels within 1-2 hr, whereas lectin (PHA) and PPD did not induce such changes. The cAMP response to endotoxin varied. Stimulation with IC induced an increase in monocyte cGMP levels, whereas the other stimulants did not cause such changes.
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PMID:Effect of cyclic AMP and cyclic GMP on thromboplastin (factor III) synthesis in human monocytes in vitro. 632 Apr 87

Human monocytes synthesize the protein component of thromboplastin and express increased procoagulant activity when appropriately stimulated in vitro. The activity reached maximum between 2 and 20 h depending on the stimulant used. The presence of lymphocytes (lymphocyte: monocyte ratio 4:1) enhanced this activity only very slightly (up to 1.3-fold) at the time of maximal monocyte thromboplastin expression. Lymphocytes had a marked potentiating effect on PHA stimulation that became clearly evident after 12 h, at which time the thromboplastin response of monocytes alone to PHA had subsided. The thromboplastin activity of monocytes remained at a high level for 24-40 h in the presence of PHA or endotoxin and lymphocytes, but lymphocytes did not influence the early (4-8 h) thromboplastin response. Neither did lymphocytes alter the magnitude or the time course of the response when monocytes were stimulated with PPD, TPA or immune complexes. The lymphoblastoid cell line Molt 4 (T cell like) was as effective as lymphocytes, Daudi cells (B cell like) were slightly less effective. The enhancement of thromboplastin activity in PHA-stimulated monocytes could be induced also by conditioned medium from PHA stimulated lymphocytes. We conclude that freshly isolated monocytes synthesize thromboplastin directly upon interaction with a stimulant, and are not dependent on a helper effect of lymphocytes or lymphocyte products. Such help, however, will prolong the ability of the monocytes to respond.
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PMID:Is lymphocyte co-operation necessary for thromboplastin synthesis by human monocytes? 661 64

Activated coagulation factor V (FVa) functions as a cofactor to factor Xa (FXa) in the conversion of prothrombin (PT) to thrombin. This essential procoagulant reaction, despite being the subject of extensive investigation, is not fully understood structurally and functionally. To elucidate the structure of the FXa-FVa complex, we have performed protein:protein (Pr:Pr) docking simulation with the pseudo-Brownian Pr:Pr docking ICM package and with the shape-complementarity Pr:Pr docking program PPD. The docking runs were carried out using a new model of full-length human FVa and the X-ray structure of human FXa. Five representative models of the FXa-FVa complex were in overall agreement with some of the available experimental data, but only one model was found to be consistent with almost all of the reported experimental results. The use of hybrid docking approach (theoretical plus experimental) is definitively important to study such large macromolecular complexes. The FXa-FVa model we have created will be instrumental for further investigation of this macromolecular system and will guide future site directed mutagenesis experiments.
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PMID:Proposed structural models of the prothrombinase (FXa-FVa) complex. 1643 49