摘要:

The interaction between blood platelets and the vessel wall represents the initial event in the haemostatic response to vessel injury. At a molecular level, this interaction involves the platelet membrane glycoprotein (GP) Ib-IX complex, von Willebrand factor (vWF) and a component (s) of the subendothelial matrix. In recent years, the primary sequences of both the vWF molecule and the three chains comprising the GP Ib-IX complex, i.e., GP Ibα, GP Ibβand GP IX, have been determined, providing further insight into the structure-function relationships of these molecules. As a result, much recent investigation has been directed towards identifying small amino acid sequences in the primary chains of both GP Ibαand vWF which define the adhesive interaction. This review summarises current data concerning structure-function analysis of vWF and the GP Ib-IX complex and the putative identification of ligand- and receptor-binding domains involved in the interaction of vWF with the GP Ib-IX complex.

ISSN:0953-7104    

DOI:10.3109/09537109009005485

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Streptokinase (SK) frequently induced platelet aggregation when added to citrated whole blood in vitro, but aggregation did not occur in corresponding samples of platelet-rich plasma (PRP). The aggregation occurred at concentrations of SK that are achieved after systemic infusion and was significantly more extensive in blood from men than women. SK-induced aggregation was accompanied by TXB2formation and release of14C-5HT and was inhibited by aspirin, by sulotroban, a TXA2antagonist, and by apyrase, an enzyme which removed ADP from plasma. Aggregation was also inhibited by each of three agents that interrupt the fibrinolytic pathway: epsilon-aminocaproic acid (ACA), aprotinin and alpha-2-antiplasmin. It is suggested that the aggregation is consequent to platelet activation by plasmin formed on the platelet surface, with ADP from red cells playing a part.In contrast to results obtained in vitro, prior administration of SK to man resulted in inhibition of the aggregation that occurs when this agent is added to whole blood. This effect was reproduced in vitro by pre-incubating blood with SK prior to carrying out aggregation studies. Similar inhibition was obtained when plasmin was added to blood and it is suggested that this effect of SK may be mediated by plasmin formed in plasma.In contrast to the pro-aggregatory effects of SK in vitro, recombinant tissue plasminogen activator (rt-PA) only inhibited platelet aggregation in whole blood. rt-PA inhibited the aggregation induced by a wide range of agents suggesting a central mechanism of action. Inhibition of aggregation was prevented by ACA, suggesting that this is also mediated by plasmin formed in plasma.The relevance of these observations is discussed in relation to the increasing use of fibrinolytic therapy in acute thrombosis in man. It is suggested that slow infusion of SK should always be performed so as to maximise the inhibitory rather than potentiatory effect of this agent on platelet aggregation, and that SK should only be used after prior administration of an anti-platelet agent.

ISSN:0953-7104    

DOI:10.3109/09537109009005486

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

In view of the evidence that unfractionated heparins (UH) cause thrombocytopenia in vivo and platelet activation in vitro, we investigated the effect of UH administration on platelet indices likely to reflect in vivo activation. Our experiments, in healthy volunteers, show that following the intravenous administration of UH: (1) platelet aggregation in whole blood is significantly enhanced; (2) platelet counts in platelet rich plasma (PRP), prepared using citrate as anticoagulant, are significantly diminished; this effect is not observed in PRP prepared from blood anticoagulated with EDTA or in the whole blood itself and (3) the modal and median platelet volume increases significantly. We conclude that some degree of platelet activation occurs after the intravenous injection of UH.

ISSN:0953-7104    

DOI:10.3109/09537109009005487

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The effect of cholesterol-enrichment in platelet membranes on U46619 binding to the specific receptor and phospholipase A2and C activities was studied using cholesterol-loaded human platelets prepared by in vitro incubation with cholesterol-rich liposomes. The cholesterol-enriched platelets, having a higher cholesterol/phospholipid molar ratio, were hyperaggregable to collagen, arachidonic acid, the thromboxane mimetic U46619 or thrombin. The number of binding sites for U46619, but not the affinity, was significantly increased. Arachidonic acid liberation from membrane phospholipids in response to collagen, thrombin or A23187 was also markedly increased. Furthermore, GTPγS-induced stimulation of the platelet membranes isolated from the cholesterol-enriched platelets, caused significantly increased arachidonic acid liberation but not increased diacyglycerol formation, as compared with the membranes from normal platelets.These results suggest that a certain physical change in cholesterol-loaded membranes brings about a hyperresponsiveness of the endoperoxide receptor and a hyperreactivity of phospholipase A2, probably through enhancement of the coupling efficiency of the corresponding GTP-binding protein to the enzyme, thereby resulting in the increased aggregability to collagen or arachidonic acid. The increased sensitivity to thrombin may be due to a factor such as an increase in thrombin binding, since phospholipase C activity was not enhanced in response to stimuli without intervention of the receptor.

ISSN:0953-7104    

DOI:10.3109/09537109009005488

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Platelet phosphoinositide metabolism was examined during platelet-fibrin clot formation stimulated by ADP (10μM) plus reptilase, or by thrombin (1 U/ml), for 120 s in the presence of fibrinogen, to determine which changes are specifically associated with this process. Stirring at 200 rpm was used to minimise the contribution of aggregation to the platelet changes. Under these conditions, thrombin caused extensive release of the contents of platelet granules; ADP plus reptilase did not. The presence of fibrinogen decreased the amount of extractable phosphatidylinositol 4,5-bisphosphate (PIP2) by 46.4±5.5% when thrombin was the stimulus, and by 47.4±5.5% when the platelets were stimulated by ADP plus reptilase. Fibrinogen did not decrease the extraction of other phospholipids. The amount of phosphatidylinositol 4-phosphate (PIP) increased when platelets were stimulated in either the presence or absence of fibrinogen. These increases were greater in the presence of fibrinogen and the thrombin-induced increase was smaller than the increase induced by ADP plus reptilase; with ADP plus reptilase, the increase in PIP more than accounted for the loss of extractable PIP2. In platelets prelabelled with [3H]inositol, the decrease in PIP2labelling induced by fibrinogen with ADP plus reptilase as the stimulus was accounted for by the increase in PIP labelling; the decrease induced by fibrinogen with thrombin as the stimulus was not. With thrombin, 46.5% of the decrease in PIP2labelling, caused by fibrinogen, was accounted for by label that remained with the interfacial protein after lipid extraction; with ADP plus reptilase, the amount of label with this protein was the same with or without fibrinogen. Only thrombin increased the amount of label in inositol trisphosphate (IP3) and the amount of phosphatidic acid (PA); these changes were not increased by fibrinogen. Thus, the results with ADP plus reptilase indicate that clot formation is not dependent on release of granule contents, formation of detectable IP3or PA (and hence does not require activation of phospholipase C) or association of [3H]inositol-labelled compounds with protein. Clot formation is associated with a shift in the PIP2-PIP equilibrium toward PIP.

ISSN:0953-7104    

DOI:10.3109/09537109009005489

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The ability of glycoprotein IIb-IIIa (GPIIb-IIIa) receptors on fully spread, surface-activated platelets to bind specific antibodies or ligands, singly or sequentially, and clear them toward cell centres has been established in several investigations. However, the basic mechanism involved in receptor-ligand translocation remains unclear. The present study has attempted to provide additional information by adding two different electron-dense probes simultaneously to surface-activated cells. Over a 5 min period of incubation small latex particles were cleared more rapidly from platelet margins to cell centres than simultaneously added particles of colloidal gold coupled to fibrinogen (Fgn/Au). Large and small latex spherules mixed together and added to spread platelets under the same conditions were moved at the same rate and concentrated together in the cell centres. Results of this investigation indicate that simple diffusion is unlikely to be the generating force for movement of receptor complexes on platelet plasma membranes.

ISSN:0953-7104    

DOI:10.3109/09537109009005490

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

ISSN:0953-7104    

DOI:10.3109/09537109009005491

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

ISSN:0953-7104    

DOI:10.3109/09537109009005492

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

ISSN:0953-7104    

DOI:10.3109/09537109009005493

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

ISSN:0953-7104    

DOI:10.3109/09537109009005494

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor