Platelets are 2.5 µm in average normal diameter and have a discod shape. The resting platelet is divided into three zones:
- Peripheral zone: responsible for adhesion and aggregation. Consists of fluffy glycocalyx coat, cytoskeleton and platelet membrane. Contains absorbed coagulation factors I, V, VIII, XI, XII, receptors for ADP, thrombin, vWF, collagen, fibrinogen, fibrin, fibronectin, epinephrine, PAF, thrombospondin, thromboxane A2, prostacyclin, epinephrine, serotonin and glycosyl transferase.
- Sol-Gel zone: responsible for contraction and support microtubule system. Contains the connecting system called the open canalicular system and the dense tubular system.
- Organelle zone: contains the dense body system, non-metabolic ADP, serotonin, catecholamines, calcium, alpha granules; platelet factor 4, platelet mitogenic factor, fibrinogen, beta thromboglobulin, lysosomal granules, mitochondria and glycogen granules.
The following animation shows more information on platelet ultrastructure:
(Requires Adobe Flash Player™. Click here for free download). (For animation uses, please seeUse of Content at Legal Information). |
| | Platelets contribute to the hemostatic process in two different ways. First, through their adhesive and cohesive functions that lead to the formation of a hemostatic plug. Second, they can activate coagulation mechanisms through the exposure of an adequate phospholipidic surface, acting as a catalytic site for the development of coagulation and the consolidation of the hemostatic plug. To promote a correct hemostasis, platelets should ideally retain their adhesive and procoagulant properties.
Platelets possess important secretory functions. During the process of activation, platelets express internal membrane proteins and release adhesive proteins, coagulation and growth factors. Some of the proteins facilitate the cross-talk of platelets with leukocytes and endothelial cells. Thus platelets play and important role in imflamatory and proliferative events and play a critical role for tissue remodeling and wound healing.
The following animation shows, step by step, the physiological process of hemostasis as it occurs in flowing blood:
(Requires Adobe Flash Player™. Click here for free download). (For animation uses, please seeUse of Content at Legal Information). |
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| | Scanning electron micrographs of different stages of platelet adhesion are shown: Resting platelet (left, x10,000); Attached platelet showing shape change and pseudopodia emission (center, x3,000); Spread platelet (right, x3,000). Click on pictures to enlarge.
(Pictures have been kindly provided by Dr. J. White. For image uses, please see Use of Content at Legal Information).
See bibliografy |
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| | Initial attachment of platelets onto vascular subendothelium is a critical step for hemostasis. Several factors are known to participate in platelet-subendothelium interactions: subendothelial and plasma adhesive proteins, their receptors on platelet membrane, and rheological factors. Alteration of any of these factors may imply disorders of physiologic hemostasis, leading to thrombosis or bleeding episodes.
Laminin, von Willebrand factor, fibronectin, and different types of collagen are the main components of subendothelial structures. It is known that the binding of von Willebrand factor to subendothelium and to platelet glycoprotein Ib is of critical importance for platelet attachment to subendothelial components. Subsequent platelet spreading and aggregate formation is mediated by platelet glycoprotein IIb-IIIa.
The contribution of platelets to hemostasis does not depend exclusively on adhesive and cohesive functions mediated by membrane receptors. Activated platelets offer a phospholipid surface of critical importance for the activation of coagulation mechanisms.
The following animations shows the process of platelet attachment on a thrombogenic surface, shape change, pseudopodia emission, spreading, adhesion and aggregation (electron micrographs of platelets have been provided by Dr. J. White):
(Requires Adobe Flash Player™. Click here for free download). (For animation uses, please seeUse of Content at Legal Information). |
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| | Electronic micrographs showing some attached and aggregating platelets on a thrombogenic surface (left, x1,000) and a cross-section of a thrombus (right, x5,000). Click on pictures to enlarge.
(Pictures have been kindly provided by Drs. J. White and G. Escolar. For image uses, please see Use of Content at Legal Information).
See bibliografy
Platelet activation takes place after attachment and adhesion events or after other stimuli that triggeres activation mechanisms such as thromboxane A2, ADP, thrombin or PAF (platelet activating factor, released from endothelial cells, PMN or monocytes).
In a first step of activation, platelets undergo shape change, cytoskeleton rearrangement and organelle centralization. Release of dense granule contents (ADP and ATP) and serotonin, occurs. In a second step, there is alpha granule release of fibrinogen, fibronectin and vWF, exposure of fibrinogen and fibronectin receptors on platelet surface, and finally, release of arachidonic acid to be converted to thromboxane A2, which is a powerful mediator of platelet aggregating response.
Cyclooxygenase is the key enzyme responsible for synthesis of thromboxane A2 in platelets. Aspirin and other anti-inflammatory drugs interfere with an early step of prostaglandin pathway, suppressing the formation of pro-aggregatory cyclic endoperoxides precursors of thromboxane A2.
The following animations show detailed information on most of the receptors, molecular mechanisms, signaling pathways and platelet responses that are triggered after activation, as well as their regulatory and modulatory mechanisms:
(Requires Adobe Flash Player™. Click here for free download). (For animation uses, please seeUse of Content at Legal Information).
It is important to point out that the information contained in the animation should not be considered as facts but models subjected to debate:
- Actin polymerization and lamellipodia formation
- Granule content secretion
- Arachidonic acid mobilization
- Phospholipid scrambling and coagulation
- PAR thrombin receptors (Gi, Gq and G12/13)
- Thromboxane A2 receptors (Gq and G12/13)
- P2Y1 and P2Y12 ADP receptors (Gi and Gq)
- Glycoprotein Ia-IIa
- Glycoprotein Ib-IX-V
- Glycoprotein IIb-IIIa
- Glycoprotein IV
- Glycoprotein VI
| | Cellular interactions between platelets and vascular endothelium or other blood cellular components regulate the hemostatic process. Platelets can even interact and play a role in the activity of pathologic elements such as tumoral cells or infectious agents. Moreover, it has been described that platelet interactions can interfere with the effectivity of antiplatelet drugs.
- Vascular endothelium: The endothelium does not form a passive barrier for blood circulation. Endothelial cells and several of their active metabolites, including eicosanoids such as prostacyclin (PGI2) and endothelial-derived relaxing factor (nitric oxide), are known to directly influence platelet reactivity.
- Leukocytes: The activating and inhibitory mechanisms triggered by the interactions between platelets and leukocytes are widely recognized. Lipoxygenase products such as HETEs and several surface glycoproteins play a role in platelet-leukocyte cross-talk, which is favored by pathophysiologic events at sites of inflammation, thrombosis and vascular injury.
- Erythrocytes: Red blood cells play an important role in modulating platelet reactivity with subendothelial structures, mainly through rheological mechanisms (i.e., erythrocyte deformability and erythrocyte aggregation), although the influence of red cell metabolites on platelet functions is also important.
- Tumoral cells: Platelet ability to interact with tumor cells is involved in the success of metastatic spread. Moreover, thrombotic events are often associated with cancer due to the capacity of tumor cells to produce and secrete procoagulant/fibrinolytic substances and inflammatory cytokines.
- Infectious agents: Platelet binding by bacterial pathogens is thought to facilitate the establishment of certain infections. Furtehrmore, association of virus with platelets may represent a viral transfer and a passive vehicle for viral dissemination.
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Left: endothelial cells in culture (micrograph by M. Diaz-Ricart); middle:platelet-leukocyte heterotypical aggregation (micrograph by M.R. Hernández) ; Right: platelet and leukocyte interaction with a tumor cell (micrograph by A. Ordinas). Click on pictures to enlarge. (For image uses, please see Use of Content at Legal Information) |
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| Electron micrographs from a resting platelet (left, x10,000), or from an activated platelet showing pseudopodia emission (right, x5,000). Click on pictures to enlarge.
(Pictures have been kindly provided by Dr. J. White. For image uses, please see Use of |
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