Interrelations of Platelet Aggregation and Secretion (original) (raw)
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Stochastic response of human blood platelets to stimulation of shape changes and secretion
Proceedings of the National Academy of Sciences, 1986
Stopped-flow turbidimetric data indicate that platelets stimulated with low levels of thrombin undergo a shape transformation from disc to "sphere" to smaller spiny sphere that is indistinguishable from the shape change induced by ADP through different membrane receptor sites and a dissimilar receptor trigger mechanism. Under conditions 2076 The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Platelet secretory behaviour: as diverse as the granules … or not?
Journal of Thrombosis and Haemostasis, 2015
Platelets play a central role in the arrest of bleeding after damage to a blood vessel and in the development of thrombosis. Platelets rapidly respond after interaction with sub‐endothelial components and release cargo from their storage granules. The three principal granule types of platelets are α‐granules, dense granules and lysosomes. Timed release of granule contents and regulated expression of critical receptors are essential for maintenance of the platelet thrombus, yet also have important functions beyond hemostasis (i.e. inflammatory reactions and immune responses). α‐granules store adhesive molecules such as von Willebrand factor and fibrinogen, growth factors and inflammatory and angiogenic mediators, which play crucial roles in inflammatory responses and tumor genesis. The α‐granules comprise a group of subcellular compartments with a unique composition and ultrastructure. Recent studies have suggested that differential secretory kinetics of α‐granule subtypes is responsible for a thematic release of adhesive and inflammatory mediators. In addition, new results indicate that activation‐dependent synthesis and release of cytokines also contribute to the inflammatory role of platelets. We will discuss the various methods that platelets use to regulate secretory processes and how these relate to potential differential secretion patterns, thereby promoting adhesiveness and/or inflammatory functions. We will focus on the heterogenic granule population, open canalicular system (OCS) plasticity, the role of contractile and mechanobiological forces, and the fusogenic machinery.
Circulation, 2001
Background —Tests developed to monitor glycoprotein (GP) IIb/IIIa blockade do not properly reflect platelet function in vivo and need a baseline (pretreatment) value. Because GP IIb/IIIa is essential in platelet aggregation and thrombosis under shear conditions, a flow-dependent approach to monitor its inhibition can be used. Methods and Results —We compared a test based on flow-dependent platelet deposition, the Cone and Platelet Analyzer (CPA), with in vitro platelet aggregometry and the Rapid Platelet Function Assay (RPFA) on platelet function after GP IIb/IIIa inhibition. In vitro, increasing concentrations of abciximab (0% to 100% receptor occupancy) were tested. Ex vivo, platelet function was monitored with the CPA and with aggregometry for up to 1 week after abciximab administration. The CPA was better correlated with the percentage of free GP IIb/IIIa receptors than was aggregometry or the RPFA. Only the RPFA, when expressed as a ratio over baseline (pretreatment), was compa...
Platelet membrane potential as a modulator of aggregating mechanisms
Biochimica et Biophysica Acta (BBA) - Biomembranes, 1988
The membrane potential of platelets suspended in physiological medium and membrane potential changes induced by high potassium ¢oncenlrations, onaba[v, and cooling have been measured using a eyanlne fluorescent dye (3,3'-dipropylthiediearboeyanide). The membrane potential of platelets suspended in physiological medium was -63.8 mV. High potassium concentrations, ouabain and cooling induced depolarization of platdet membrane. Depolarization using the above procedures enhanced platelet aggregation induced by ADP~ adrenalL~e and collagen. These results suggest that the membrane potential could moduhle lflatelet activity.
Platelet response heterogeneity in thrombus formation
Thrombosis and haemostasis, 2009
Vascular injury leads to formation of a structured thrombus as a consequence of platelet activation and aggregation, thrombin and fibrin formation, and trapping of leukocytes and red cells. This review summarises current evidence for heterogeneity of platelet responses and functions in the thrombus-forming process. Environmental factors contribute to response heterogeneity, as the platelets in a thrombus adhere to different substrates, and sense specific (ant)agonists and rheological conditions. Contraction of platelets and interaction with fibrin and other blood cells cause further response variation. On the other hand, response heterogeneity can also be due to intrinsic differences between platelets in age and in receptor and signalling proteins. As a result, at least three subpopulations of platelets are formed in a thrombus: aggregating platelets with (reversible) integrin activation, procoagulant (coated) platelets exposing phosphatidylserine and binding coagulation factors, an...
Arteriosclerosis, Thrombosis, and Vascular Biology, 2005
Objective— Previous work has shown that platelets stimulated with the combination of thrombin and convulxin, a glycoprotein VI agonist, develop 2 populations with different levels of α-granule factor V bound to the platelet surface. To evaluate whether this phenomenon is restricted to α-granule components or is a feature that can be generalized to other coagulation factors, we studied the binding of factors V, VIII, IX, and X on the surface of platelets stimulated by convulxin and thrombin. Methods and Results— The relative amount of factors V, VIII, IX, and X on the surface of platelets stimulated with thrombin or convulxin plus thrombin was measured using flow cytometry. Simultaneous measurements of factor Xa and thrombin generation were obtained and correlated with the binding of coagulation factors on the platelet surface. The binding of factors V, VIII, IX, and X all increased on a subpopulation of platelets when stimulated with the combined agonists. The development of this pl...
A New Method for Measuring the Dynamic Shape Change of Platelets
Transfusion Medicine and Hemotherapy, 2010
Background: Platelet shape change is a dynamic process that has been classified in different types. Exact documentation of platelet structure needs an improved method of measuring platelet shape. Methods: 10 μl of platelet-rich plasma (PRP) from anticoagulated whole blood (3.2% buffered sodium citrate 0.105 mol/l) was put onto a glass slide covered with a cover slip. By use a of dark field light microscope connected with a CMOS-Camera a photographic snapshot was taken after 5 and 30 min. Diameter of platelets and length of filopodia were measured with a self-developed plugin for ImageJ software. Statistic calculation was performed with Excel WinSTAT Microsoft software. Results: We showed a swelling of the granulomer from 2.06 ± 0.56 μm to 2.33 ± 0.59 μm (p < 0.05), a reduction of pseudopodia (2.10 ± 0.94 vs. 1.78 ± 1.04 μm; p < 0.05) in conjunction with an increase of hyalomer diameter from 3.29 ± 0.83 to 3.50 ± 0.85 μm (p < 0.05), and an increase of pseudopodia length from 2.68 ± 1.45 μm to 3.67 ± 1.79 μm (p < 0.005) in conjunction with an increase of hyalomer diameter from 6.58 ± 1.91 μm to 7.94 ± 1.87 μm (p < 0.05). Conclusion: We revealed and documented a dynamic change of platelet size and filopodia structure in PRP. This method allows an exact analysis of platelet size and surface structures. Irfan View software Version 4.00. Statistical Analysis Statistical calculation was performed with the Excel WinSTAT Microsoft software (Version 2009.1, Windows 2000). The data of the platelet para meters were displayed as mean and standard deviation.
Investigation of shear dependent platelet aggregation
2017
Statement of Originality I, Elham Tolouei declare that this thesis is my own work and contains no material that has been accepted for the award of a degree or diploma in this, or any other, university. To the best of my knowledge and belief, information derived from the published and unpublished work of others has been acknowledged in the text of the thesis and a list of references is provided in the bibliography.