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1.
M. P. MAHAUT‐SMITH 《Journal of thrombosis and haemostasis》2012,10(9):1722-1732
Summary. Ion channels are transmembrane proteins that play ubiquitous roles in cellular homeostasis and activation. In addition to their recognized role in the regulation of ionic permeability and thus membrane potential, some channel proteins possess intrinsic kinase activity, directly interact with integrins or are permeable to molecules up to ≈1000 Da. The small size and anuclear nature of the platelet has often hindered progress in understanding the role of specific ion channels in hemostasis, thrombosis and other platelet‐dependent events. However, with the aid of transgenic mice and ‘surrogate’ patch clamp recordings from primary megakaryocytes, important unique contributions to platelet function have been identified for several classes of ion channel. Examples include ATP‐gated P2X1 channels, Orai1 store‐operated Ca2+ channels, voltage‐gated Kv1.3 channels, AMPA and kainate glutamate receptors and connexin gap junction channels. Furthermore, evidence exists that some ion channels, such as NMDA glutamate receptors, contribute to megakaryocyte development. This review examines the evidence for expression of a range of ion channels in the platelet and its progenitor cell, and highlights the distinct roles that these proteins may play in health and disease. 相似文献
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Bassini A Pierpaoli S Falcieri E Vitale M Guidotti L Capitani S Zauli G 《British journal of haematology》1999,104(4):820-828
Mammalian megakaryocyte development is characterized by a progressive accumulation of cells exhibiting a polylobated nucleus with a polyploid DNA content. In this study human megakaryocytes were obtained from CD34+ haemopoietic progenitors by in vitro liquid culture in the presence of 100 ng/ml of recombinant thrombopoietin (TPO). Ultrastructural examination of polyploid megakaryocytes showed the presence of a large number of centrioles, the breakdown of the nuclear envelope, and the progressive chromatin condensation, all aspects characteristic of mitosis. At both indirect immunofluorescence and Western blot analyses, cyclin B and its related cyclin-dependent kinase (CDK)1, which forms the mitosis promoting factor (MPF), showed an increased expression in maturating megakaryoblasts and megakaryocytes (day 8 of culture) with respect to freshly isolated CD34+ progenitors. This expression tended to decline in fully developed megakaryocytes (day 15 of culture). The amount of cyclin D and of the related CDK4, governing the G1 phase of the cell cycle, increased during megakaryocyte development, maintaining high levels of expression also in mature megakaryocytes. These results indicate that megakaryocyte polyploidization depends on a true, although incomplete, mitotic process, and that cyclin D/CDK4 probably plays a crucial role throughout megakaryocytopoiesis. 相似文献
4.
Fraxiparin, a low-molecular-weight heparin, stimulates megakaryocytopoiesis in vitro and in vivo in mice 总被引:1,自引:0,他引:1
Z. X. Shen N. Basara X. D. Xi J. Caen J. P. Maffrand M. Pascal M. Petitou J. C. Lormeau Z. C. Han 《British journal of haematology》1994,88(3):608-612
Summary. The effect of a low-molecular-weight heparin, faxiparin (Nadroparinŕ;), on murine megakaryocytopoiesis in vitro and in vivo was studied in comparison with unfractionated heparin. The addition of fraxiparin at 1–20 IU/ml into plasma clot cultures but not serum-free agar culture significantly enhanced MK colony growth. Furthermore, fraxiparin was found to potentiate the stimulating activity of aplastic anaemia serum (AAS) but not stem cell factor (SCF), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo), on MK colony growth in vitro , and to neutralize the inhibitory effect of platelet factor 4 (PF4) in vitro and in vivo . Fraxiparin also acted synergistically with heparin confactor II and antithrombin III to promote megakaryocyte colony formation. Intraperitoneal administration of fraxiparin twice daily for 4d at 0.1–25IU/injection increased in mice the level of blood platelet counts and the number of single MKs and CFU-MK in bone marrow. These data demonstrate that fraxiparin is able to positively regulate megakaryocytopoiesis. 相似文献
5.
Omar Bauomy Ahmed Usama Taha Mahmoud Sara Elganady Allam Mohamed Nafady Salah Mohamed Hassan Afifi 《Ultrastructural pathology》2016,40(6):342-350
Silver nanoparticles (SNP) are used in many pharmaceutical, cosmetic, and industrial products already available in the market. Although they are considered relatively safe, many toxic and pathological alterations in different organs including immune organs were reported after SNP administration. In this study, 10-week-old male mice (n = 20) were divided into two groups. Ten mice received greenly synthesized gelatin-coated silver nanoparticles in a dose of 10 mg/kg body weight for five consecutive days while the other 10 received 0.5 ml of distilled water daily for 5 days and kept as control. At the sixth day, all mice were sacrificed; blood and tissue samples were collected and prepared for pathological analysis. Liver and kidney lesions were in the form of degenerative and inflammatory changes. Interestingly, the immune organs were drastically affected by SNP treatment. Severe hyperplasia of the Peyer’s patches was noticed in the intestines of intoxicated animals both in gross and microscopic examination. Spleen was enlarged and showed large number of megakaryocytes. The particles were encountered in membrane-bound phagosomes inside macrophages in different organs like lungs and spleen. Blood picture complied to morphological findings with an increase in monocytes and eosinophils accompanied by drop in the platelets count in the intoxicated animals. 相似文献
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An unusual case of severe thrombocytopenia following acetaminophen overdose is pre sented along with a retrospective review of 174 patients with hospital admissions for acute acetaminophen toxicity. Thrombocytopenla occurred in 3.4% of these patients and strongly correlated with the degree of hepatotoxicity (as measured by peak AST values) but did not correlate with serum acetaminophen levels. The mechanism appears to be a transient direct toxic effect on platelets or megakaryocytes, and the finding of thrombocytopenia early in the course of acetaminophen overdose may identify a subset of patients at risk for significant hepatotoxicity. © 1994 Wiley-Liss, Inc. 相似文献
8.
《Journal of anatomy》2017,230(2):337-346
Spinal muscular atrophy (SMA), traditionally described as a predominantly childhood form of motor neurone disease, is the leading genetic cause of infant mortality. Although motor neurones are undoubtedly the primary affected cell type, the severe infantile form of SMA (Type I SMA) is now widely recognised to represent a multisystem disorder where a variety of organs and systems in the body are also affected. Here, we report that the spleen is disproportionately small in the ‘Taiwanese’ murine model of severe SMA (Smn−/−;SMN2tg/0), correlated to low levels of cell proliferation and increased cell death. Spleen lacks its distinctive red appearance and presents with a degenerated capsule and a disorganised fibrotic architecture. Histologically distinct white pulp failed to form and this was reflected in an almost complete absence of B lymphocytes necessary for normal immune function. In addition, megakaryoctyes persisted in the red pulp. However, the vascular density remained unchanged in SMA spleen. Assessment of the spleen in SMA patients with the infantile form of the disease indicated a range of pathologies. We conclude that development of the spleen fails to occur normally in SMA mouse models and human patients. Thus, further analysis of immune function is likely to be required to fully understand the full extent of systemic disease pathology in SMA. 相似文献
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The relationship between fibrosis and megakaryocytic infiltration in the lungs of patients with Philadelphia-chromosome (Ph1)-positive chronic myelogenous leukemia (CML) is the focus of this review. Ph1-positive megakaryocytes are thought to reach and accumulate in the pulmonary vasculature through the marrow-blood barrier. In 21 autopsied patients with accelerated phase or blastic crisis of CML, megakaryocytic infiltration to the lungs was demonstrated in 10 patients, myelofibrosis in 12 patients and both in 5 patients. In 2 of the 10 patients with increased megakaryocytes in the lungs, relatively new fibrosis and alveolar damage in the acute phase were demonstrated with the simultaneous occurrence of myelofibrosis-“myelopulmonary fibrosis.” Leakage of mitogenic factors resulting from an abnormality in the packaging mechanism of alpha-granules in these cells termed acquired grey platelet syndrome could cause Fibrosis in the lungs as well as the bone marrow. 相似文献