Platelets Megakaryocytes

CD141 (thrombo- modulin) Mesothelioma, transitional cell carcinoma Squamous cell carcinoma, trophoblastic tumors, vascular tumors, synovial sarcoma Endothelial cells, urothelium, mesothelial cells, keratinizing epithelial cells, meningeal lining cells, platelets/ megakaryocytes, monocytes, neutrophils, smooth muscle cells, syncytiotrophoblasts, synovial lining cells... 

Thrombopoietic factors (no recombinant TPO product in clinical use at this time IL-11 [recombinant product oprelvekin] has marketing approval) stimulate the production of megakaryocyte precursors, megakaryocytes, and platelets [8]. Interleukin-11 has many effects on multiple tissues, and can interact with IL-3, TPO, and SCF. AMG 531, a recombinant peptibody in that binds to the thrombopoetin receptor Mpl and stimulates the production of platelets, is in phase 1 and 2 studies and has been shown to safely increase platelet counts in patients with immune thrombocytopenic purpura [9]. 

Platelets are the formed elements of the blood which participate in hemostasis. Platelets are enucleated, discoid fragments which arise from mature megakaryocytes in the bone marrow. Under normal circumstances, platelets do not adhere to endothelial surfaces of blood vessels. However, platelets can adhere to damaged areas of blood vessels and become activated in such a way that they can also bind fibrinogen. 

The von Willebrand factor (vWf) is a heterogeneous multimeric plasma glycoprotein produced by megakaryocytes and endothelial cells which is found in platelets, plasma and the subendothelium. Subendothelial vWf facilitates platelet adhesion, especially under high shear stress, by binding to glycoprotein GPIb-V-IX, a complex of four leucine-rich repeat proteins on platelets. 

Blood platelets are key players in the blood-clotting mechanism. These tiny fragments of cytoplasm are shed into the circulation from the surface of megakaryocytes located in the bone marrow. When the lining of a blood vessel is injured, activated platelets release clotting factors, adhere to each other and to damaged surfaces, and send out numerous filopodia. The shape changes that occur in activated platelets are the result of actin polymerization. Before activation, there are no microfilaments because profilin binds to G-actin and prevents its polymerization. After activation, profilin dissociates from G-actin, and bundles and networks of F-actin filaments rapidly appear within the platelet. 

IgG autoantibody-coated platelets induce Fey receptor-mediated phagocytosis by mononuclear macrophages, predominantly in the spleen and liver. Thrombocytopenia develops as a consequence of megakaryocyte inability to increase platelet production and maintain a normal number of circulating platelets. Currently used treatments are directed at different aspects of the antibody production, platelet sensitization, and the clearance and production cycle.30... 

Hematopoiesis is defined as the development and maturation of blood cells and their precursors. In utero, hematopoiesis may occur in the liver, spleen, and bone marrow. However, after birth, it occurs exclusively in the bone marrow. All blood cells are generated from a common hematopoietic precursor, or stem cell. These stem cells are self-renewing and pluripotent and thus are able to commit to any one of the different lines of maturation that give rise to platelet-producing megakaryocytes, lymphoid, erythroid, and myeloid cells. The myeloid cell line produces monocytes, basophils, neutrophils, and eosinophils, whereas the lymphoid stem cell differentiates to form circulating B and T lymphocytes. In contrast to the ordered development of normal cells, the development of leukemia seems to represent an arrest in differentiation at an early phase in the continuum of stem cell to mature cell.1... 

PLATELETS. Platelets are nonnucleated discoid or elliptical cells that originate from the fragmentation of giant polyploid megakaryocytes located in the bone marrow. The average diameter of the platelet is 1.5 pm. Each platelet is surrounded by a trilaminar membrane, and its cytoplasm contains a dense body (delta granule), a surface-connected canalicular system,... 

The third of the cellular elements within the blood are the platelets (thrombocytes). Platelets are actually small, round or oval cell fragments. They are about 2 to 4 pm in diameter and have no nuclei. Platelets are formed in the red bone marrow as pinched-off portions of the very large megakaryocytes. Each megakaryocyte, which is confined to the bone marrow, can produce... 

CSFs, which play a major role in the differentiation of stem-derived cells into neutrophils, macrophages, megakaryocytes (from which platelets are derived), eosinophils and basophils ... 

Figure 10.6 Simplified representation of the production of platelets from stem cells. CFU-megakaryocytes and in particular, mature megakaryocytes, are most sensitive to the stimulatory actions of TPO. These two cell types also display a limited response to IL-6, IL-11 and LIF...

P2Y receptors are activated by adenine and uridine nucleotides. Most of the known P2Y receptors have been detected in the nervous system [21]. The majority of P2Y receptors inhibit neuronal N-type Ca2+ channels and M-type K+ channels. P2Y1 receptors are found exclusively on platelets, on their precursor megakaryocyte cells and on certain other cultured hematopoietic cells, such as K562 leukemia cells. They can be distinguished from other P2 receptors in that ADP is the most potent natural agonist and ATP is a competitive antagonist. ADP acts via a G protein to inhibit cyclic AMP accumulation, mobilize intracellular Ca2+ and stimulate granule secretion. ADP... 

Platelets (also called thrombocytes), the smallest of the formed elements of the blood, are formed by fragmentation of megakaryocytes. Each megakaryocyte (mega = big , karyo = nucleus ) can produce approximately 3000 individual platelets and a total of about 2 x 1011 platelets are formed each day. 

In addition to fully differentiated cells, many tissues of the body contain stem cells - precursor cells that are not fully differentiated. These can divide to produce more stem cells but can also give rise to progeny which can differentiate. Stem cells in the bone marrow, for example, give rise to all the different types of immune cells, erythrocytes and megakaryocytes, which give rise to platelets. 

Sequential determination of platelet counts in patients receiving vincristine during early studies unexpectedly occasionally revealed thrombocytosis, which could not be accounted for by systemic response to treatment alone 10,11). Ultimately shown to most likely be the result of increased megakaryocytic endomitosis II), the observation led to the use of vincristine, and later vinblastine, both alone and bound to platelets, in a variety of thrombocytopenic disorders. These include idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, and chemotherapy-induced microangiopathic hemolytic anemia. 

Idiopathic thrombocytopenic purpura is an immune-mediated disease in which immunoglobulin, either as antibody directed against platelet antigens or nonspecifically bound to platelets, is present in increased quantities on platelets. This leads to increased destruction of platelets and, in many instances, megakaryocytes. Standard treatment consists of corticosteroids and splenectomy (72). When these measures fail, treatment may include androgenic steroids, administration of intravenous 7-globulin, or injection of vinca alkaloids. 

Platelets originate by budding off from multinucleate precursor cells, the megakaryocytes. As the smallest formed element of blood (dia. 1 -4 pm), they can be activated by various stimuli. Activation entails an alteration in shape and secretion of a series of highly active substances, including serotonin, platelet activating factor (PAF), ADP, and thromboxane A2. In turn, all of these can activate other platelets, which explains the explosive nature of the process. 

Platelets and Megakaryocytes, Volume 2 Perspectives and Techniques, edited by Jonathan M. Gibbins and Martyn P. Mahaut-Smith, 2004 272. Platelets and Megakaryocytes, Volume 1 Functional Assays, edited by Jonathan M. Gibbins and Martyn P. Mahaut-Smith, 2004 271. B Cell Protocols, edited by Hua Gu and Klaus Rajewsky, 2004... 

Fetchner syndrome Ultrastructural changes in megakaryocytes smaller cytoplasmic inclusions in platelets... 

Dense granule storage pool deficiency Deficiency of dense granules in megakaryocytes and platelets... 

Heynen, J. M., Blockmans, D., Verwilghen, L. R., et al, Congenital macrothrombocytopenia, leukocyte inclusions, deafness and proteinuria Functional and electronmicroscopic observations on platelets and megakaryocytes. Br. J. Haematol. 70, 441—448 (1998). 

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