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User:Kaguya-Taketori/巨核細胞

维基百科，自由的百科全书
巨核细胞
巨核细胞
骨髓中的巨核细胞
标识字符
拉丁文megakaryocytus
《解剖學術語》

巨核細胞（mega- + karyo- + -cyte）是一種大型的骨髓細胞。它有一個負責製造血小板（一種爲正常的凝血過程所必須的物質）的分葉狀細胞核。一般情況下，每10000個骨髓細胞中會有一個巨核細胞，但是當肌體患上某些疾病時，巨核細胞的數目可以增加近10倍[1]。

結構

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一般說來，巨核細胞的大小是紅細胞的10-15倍，其平均直徑可達50-100微米（μm）。巨核細胞在發育過程中，細胞大小會不斷增加，DNA會在不進行有絲分裂的前提下不斷複製。因爲DNA的不斷複製，巨核細胞的細胞核會變得很大，而且呈現分葉狀。如果用光鏡觀察的話，觀察者很容易誤認爲巨核細胞有多個細胞核。有時，巨核細胞的細胞核中染色體可達64組（人的一個染色體組有23條染色體，正常人的體細胞中含有2個染色體組）。

巨核細胞的細胞質基質中含有α顆粒以及。血小板可以認爲是從巨核細胞上單獨分離出來的小塊細胞質。

巨核細胞的發育

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血細胞的生成
血細胞的生成

巨核細胞可由造血幹細胞（一類具有全能性的細胞，可根據接收到的信號的不同分化爲不同的血細胞）在骨髓內分化而來。促血小板生成素（Thrombopoietin，簡稱TPO）可以誘導造血幹細胞分化爲巨核細胞，但也有其它可達到同樣的效果的途徑[2]，比如說GM-CSF、IL-3、IL-6、IL-11、趨化因子SDF-1、FGF-4[3]、促紅細胞生成素都可以誘導造血幹細胞分化爲巨核細胞[4]。巨核細胞的發育過程如下：

造血幹細胞->原始巨核細胞->前巨核細胞->巨核細胞

造血幹細胞分化爲巨核細胞後會喪失分裂能力。但是，巨核細胞卻能夠在不分裂的情況下持續進行生長和DNA複製[4]。人的巨核細胞染色體組數可達64組，而老鼠的巨核細胞染色體組數則可達256組（人和老鼠都是二倍體，即正常情況下體細胞內有2個染色體組）。如果誘導非造血細胞表達第六類β微管蛋白（β6）的話，相關細胞也會表現出不少爲巨核細胞分化所特有的形態特徵。這一事實可以幫助人們更好地理解造血幹細胞分化形成巨核細胞的過程[5]。

釋放血小板

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巨核細胞在成熟過程中，會在不分裂的情況下對核DNA進行複製。巨核細胞在完全成熟後，就會開始製造血小板[6]。促血小板生成素能夠誘導巨核細胞產生血小板。尚未被釋放的血小板被裹在巨核細胞細胞質基質內的膜中。目前，學者總共提出了兩種血小板可能的釋放機制。其中一種假說認爲，巨核細胞通過讓這些膜解體來釋放膜內的血小板[7]。該假說還指出，巨核細胞也能把一種血小板細帶釋放到血管中。這種細帶帶有僞足，並能持續地把血小板送入血液循環中。另一種假說則認爲，上述的血小板形成過程一次能夠產生2000-5000個新的血小板。

新產生的血小板有2/3會進入血循環中，另外1/3則會被脾臟暫時儲存起來。

在產生了一定數量的血小板後，巨核細胞就只剩下細胞核了。這樣的巨核細胞會穿過骨髓的血液屏障，進入肺中，然後被肺泡巨噬細胞消化掉。

Effects of cytokines

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Cytokines are signals used in the immune system for intercellular communication. There are many cytokines that affect megakaryocytes. Certain cytokines such as IL-3, IL-6, IL-11, LIF, erythropoietin, and thrombopoietin all stimulate the maturation of megakaryocytic progenitor cells.[8] Other signals such as PF4, CXCL5, CXCL7, and CCL5 inhibit platelet formation.[9]

Thrombopoietin

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主条目：thrombopoietin

Thrombopoietin (TPO) is a 353-amino acid protein located on chromosome 3p27. TPO is primarily synthesized in the liver[10] but can be made by kidneys, testes, brain, and even bone marrow stromal cells. It has high homology with erythropoietin. It is essential for the formation of an adequate quantity of platelets. Mice lacking TPO or the TPO receptor (Mpl) have a 90% reduction in circulating platelet number, although the platelets are normal in morphology and function.[11]

Disorders involving megakaryocytes

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Megakaryocytes are directly responsible for producing platelets, which are needed for the formation of a thrombus, or blood clot. There are several diseases that are directly attributable to abnormal megakaryocyte function or abnormal platelet function.[12]

Essential Thrombocythemia

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Essential thrombocytosis (ET-Also known as Essential thrombocythemia) is a disorder characterized by extremely high numbers of circulating platelets. The disease occurs in 1-2 per 100,000 people. The current WHO requirements for diagnosis include > 600,000 platelets/μL of blood (normal 150,000-400,000) and a bone marrow biopsy. Some of the consequences of having such high numbers of platelets include thrombosis or clots throughout the body. Thrombi form more frequently in arteries than veins. It seems ironic that having platelet counts above 1,000,000 platelets/μL can lead to hemorrhagic events.[13] Recent evidence suggests that the majority of ET cases are due to a mutation in the JAK2 protein, a member of the JAK-STAT pathway.[14] Evidence suggests that this mutation renders the megakaryocyte hypersensitive to thrombopoietin and causes clonal proliferation of megakaryocytes. There is a significant risk of transformation to leukemia with this disorder. The primary treatment consists of anagrelide or hydroxyurea to lower platelet levels.

Congenital amegakaryocytic thrombocytopenia (CAMT)

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Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare inherited disorder. The primary manifestations are thrombocytopenia and megakaryocytopenia, i.e. low numbers of platelets and megakaryocytes. There is an absence of megakaryocytes in the bone marrow with no associated physical abnormalities.[15] The cause for this disorder appears to be a mutation in the gene for the TPO receptor, c-mpl, despite high levels of serum TPO.[16][17] In addition, there may be abnormalities with the central nervous system including the cerebrum and cerebellum that could cause symptoms.[16] The primary treatment for CAMT is bone marrow transplantation.

Bone marrow/stem cell transplant is the only remedy for this genetic disease. Frequent platelet transfusions are required to keep the patient from bleeding to death until transplant has been completed, although this is not always the case.

One of the few non-medical research related sources on the web with some information on CAMT is:

There appears to be no generic resource for CAMT patients on the web and this is potentially due to the rarity of the disease.

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  1. ^ Branehog I, Ridell B, Swolin B, Weinfeld A. Megakaryocyte quantifications in relation to thrombokinetics in primary thrombocythaemia and allied diseases. Scand. J. Haematol. 1975, 15 (5): 321–332. PMID 1060175. doi:10.1111/j.1600-0609.1975.tb01087.x. 
  2. ^ Bunting S, Widmer R, Lipari T, Rangell L, Steinmetz H, Carver-Moore K, Moore MW, Keller GA, de Sauvage FJ. Normal platelets and megakaryocytes are produced in vivo in the absence of thrombopoietin. Blood. November 1997, 90 (9): 3423–3429. PMID 9345025. 
  3. ^ Avecilla ST, Hattori K, Heissig B, Tejada R, Liao F, Shido K, Jin DK, Dias S, Zhang F, Hartman TE, Hackett NR, Crystal RG, Witte L, Hicklin DJ, Bohlen P, Eaton D, Lyden D, de Sauvage F, Rafii S. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nat Med. January 2004, 10 (1): 64–71. PMID 14702636. doi:10.1038/nm973. 
  4. ^ 4.0 4.1 Deutsch VR, Torner A. Megakaryocyte development and platelet production. Brit. J. Haem. September 2006, 134 (5): 453–466. PMID 16856888. doi:10.1111/j.1365-2141.2006.06215.x. 
  5. ^ Yang, H; Ganguly, A; Cabral, F. Megakaryocyte Lineage Specific Class VI β-Tubulin Suppresses Microtubule Dynamics, Fragments Microtubules, and Blocks Cell Division.. Cytoskeleton. 2012, 68 (3): 175–187. PMID 21309084. doi:10.1002/cm.20503. 
  6. ^ January 2013 Megakaryocyte and Platelet Production 请检查|url=值 (帮助). 
  7. ^ Choi ES, Nichol JL, Hokom MM; et al. Platelets generated in vitro from proplatelet-displaying human megakaryocytes are functional. Blood. 1995, 85 (2): 402–13. PMID 7529062. 
  8. ^ Gordon MS, Hoffman R. Growth factors affecting human thrombocytopoiesis: potential agents for the treatment of thrombocytopenia. Blood. 1992, 80 (2): 302–307. PMID 1627792. 
  9. ^ Pang L, Weiss MJ, Poncz M. Megakaryocyte biology and related disorders. J. Clin. Invest. 2005, 115 (12): 3332–3338. PMC 1297258 可免费查阅. PMID 16322777. doi:10.1172/JCI26720. 
  10. ^ Jelkmann W. The role of the liver in the production of thrombopoietin compared with erythropoietin. Eur. J. Gastroenterol. Hepatol. 2001, 13 (7): 791–801. PMID 11474308. doi:10.1097/00042737-200107000-00006. 
  11. ^ Murone M, Carpenter DA, de Sauvage FJ. Hematopoietic deficiencies in c-mpl and TPO knockout mice. Stem Cells. 1998, 16 (1): 1–6. PMID 9474742. doi:10.1002/stem.160001. 
  12. ^ Nurden AT. Qualitative disorders of platelets and megakaryocytes. J. Thromb. And Haem. 2005, 3 (8): 1773–1782. PMID 16102044. doi:10.1111/j.1538-7836.2005.01428.x. 
  13. ^ Michiels JJ, Berneman ZN, Schroyens W, Van Vliet HH. Pathophysiology and treatment of platelet-mediated microvascular disturbances, major thrombosis and bleeding complications in essential thrombocythaemia and polycythaemia vera. Platelets. 2004, 15 (2): 67–84. PMID 15154599. doi:10.1080/09537100310001646969. 
  14. ^ Kralovics R, Passamonti F, Buser AS, Teo SS; et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005-04-28, 352 (17): 1779–90. PMID 15858187. doi:10.1056/NEJMoa051113. 
  15. ^ Freedman MH, Estrov Z. Congenital amegakaryocytic thrombocytopenia: an intrinsic hematopoietic stem cell defect. Am. J. Pediatr. Hematol. Oncol. 1990, 12 (2): 225–230. PMID 2378417. doi:10.1097/00043426-199022000-00020. 
  16. ^ 16.0 16.1 Ihara K, Ishii E, Eguchi M, Takada H, Suminoe A, Good RA, Hara T. Identification of mutations in the c-mpl gene in congenital amegakaryocytic thrombocytopenia. Proc. Natl. Acad. Sci. 1999, 96 (6): 3133–6. PMC 15907 可免费查阅. PMID 10077649. doi:10.1073/pnas.96.6.3132. 
  17. ^ Ballmaier M, Germeshausen M, Schulze H, Cherkaoui K, Lang S, Gaudig A, Krukemeier S, Eilers M, Strauss G, Welte K. C-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia. Blood. 2001, 97 (1): 139–46. PMID 11133753. doi:10.1182/blood.V97.1.139. 
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