| Contributions of TRAIL-mediated megakaryocyte apoptosis to impaired megakaryocyte and platelet production in immune thrombocytopenia. | |
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MedLine Citation:
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PMID: 20671119 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recent in vitro studies provide evidence for autoantibody-induced suppression of megakaryocytopoiesis and show a reduction in megakaryocyte production and maturation in the presence of immune thrombocytopenia (ITP) plasma. Here, we present CD34(+) cells from healthy umbilical cord blood mononuclear cells cultured in medium containing thrombopoietin, stem cell factor, interleukin-3, and 10% plasma from either ITP patients or healthy subjects. The quantity, quality, and apoptosis of megakaryocytes were measured. We observed that most ITP plasma boosted megakaryocyte quantity but impaired quality, resulting in significantly less polyploidy cells (N ≥ 4) and platelet release. In these megakaryocytes, we found a lower percentage of cell apoptosis, a lower expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and a higher expression of Bcl-xL. Furthermore, there was a decrease of sTRAIL in ITP plasma and in cell culture supernatants of this group compared with the control group. Our findings suggest that decreased apoptosis of megakaryocytes also contributes to in vitro dysmegakaryocytopoiesis and reduced platelet production. The abnormal expression of sTRAIL in plasma and TRAIL and Bcl-xL in megakaryocytes may play a role in the pathogenesis of impaired megakaryocyte apoptosis in ITP. |
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Authors:
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Lei Yang; Lin Wang; Chun-Hong Zhao; Xiao-Juan Zhu; Yu Hou; Peng Jun; Ming Hou |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-29 |
Journal Detail:
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Title: Blood Volume: 116 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-22 Completed Date: 2010-12-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 4307-16 Citation Subset: AIM; IM |
Affiliation:
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Hematology Oncology Centre, Qilu Hospital, Shandong University, Jinan, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Apoptosis* Blood Platelets / pathology* Caspase 3 / metabolism Caspase 8 / metabolism Cell Differentiation Cells, Cultured Cyclin B1 / metabolism Cyclin D3 / metabolism Female Humans Immunoglobulin G / immunology Male Megakaryocytes / enzymology, pathology* Middle Aged Solubility TNF-Related Apoptosis-Inducing Ligand / metabolism* Thrombocytopenia / blood, enzymology, immunology*, pathology* Young Adult bcl-X Protein / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Cyclin B1; 0/Cyclin D3; 0/Immunoglobulin G; 0/TNF-Related Apoptosis-Inducing Ligand; 0/TNFSF10 protein, human; 0/bcl-X Protein; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 8 |
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