title: Contributions of TRAIL-mediated megakaryocyte apoptosis to impaired megakaryocyte and platelet production in immune thrombocytopenia.
abstract: 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.
authors.affiliation: Hematology Oncology Centre, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Zhao
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Zhu
authors.forename: Yu
authors.initials: Y
authors.lastname: Hou
authors.forename: Peng
authors.initials: P
authors.lastname: Jun
authors.forename: Ming
authors.initials: M
authors.lastname: Hou
mesh_terms: D000328:Adult; D017209:Apoptosis; D001792:Blood Platelets / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D056744:Cyclin B1 / Q000378:metabolism; D056743:Cyclin D3 / Q000378:metabolism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008533:Megakaryocytes / Q000201:enzymology / Q000473:pathology*; D008875:Middle Aged; D012995:Solubility; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D013921:Thrombocytopenia / Q000097:blood / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D055815:Young Adult; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D056744:Cyclin B1; D056743:Cyclin D3; D007074:Immunoglobulin G; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D051020:bcl-X Protein; D053148:Caspase 3; D053181:Caspase 8