Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura
| Autor: | Johannes J. L. van der Want, Nel R. Blom, H Louwes, Ewout J. Houwerzijl, J.J. Koornstra, Joost Th. M. de Wolf, Mariet T. Esselink, Jan W. Smit, Edo Vellenga |
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| Přispěvatelé: | Guided Treatment in Optimal Selected Cancer Patients (GUTS), Stem Cell Aging Leukemia and Lymphoma (SALL) |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty DISORDERS Immunology CD34 THROMBOKINETICS Antigens CD34 Apoptosis Biology Biochemistry Megakaryocyte Antigens CD Reference Values immune system diseases Internal medicine hemic and lymphatic diseases medicine COLONY FORMATION Humans Platelet SPLENECTOMY Thrombopoiesis Cells Cultured GLYCOCALICIN Megakaryocytopoiesis Purpura Thrombocytopenic Idiopathic Stem Cells Cell Biology Hematology IN-VITRO medicine.disease Thrombocytopenic purpura Immunohistochemistry Haematopoiesis Microscopy Electron medicine.anatomical_structure Endocrinology AUTOIMMUNE HEMOLYTIC-ANEMIA CELL-DEATH PLATELET PRODUCTION ITP Female Bone marrow Megakaryocytes |
| Zdroj: | Blood, 103(2), 500-506. AMER SOC HEMATOLOGY |
| ISSN: | 0006-4971 |
| Popis: | To investigate whether altered megakaryocyte morphology contributes to reduced platelet production in idiopathic thrombocytopenic purpura (ITP), ultrastructural analysis of megakaryocytes was performed in 11 ITP patients. Ultrastructural abnormalities compatible with (para-)apoptosis were present in 78% ± 14% of ITP megakaryocytes, which could be reversed by in vivo treatment with prednisone and intravenous immunoglobulin. Immunohistochemistry of bone marrow biopsies of ITP patients with extensive apoptosis showed an increased number of megakaryocytes with activated caspase-3 compared with normal (28% ± 4% versus 0%). No difference, however, was observed in the number of bone marrow megakaryocyte colony-forming units (ITP, 118 ± 93/105 bone marrow cells; versus controls, 128 ± 101/105 bone marrow cells; P = .7). To demonstrate that circulating antibodies might affect megakaryocytes, suspension cultures of CD34+ cells were performed with ITP or normal plasma. Morphology compatible with (para-)apoptosis could be induced in cultured megakaryocytes with ITP plasma (2 of 10 samples positive for antiplatelet autoantibodies). Finally, the plasma glycocalicin index, a parameter of platelet and megakaryocyte destruction, was increased in ITP (57 ± 70 versus 0.7 ± 0.2; P = .009) and correlated with the proportion of megakaryocytes showing (para-) apoptotic ultrastructure (P = .02; r = 0.7). In conclusion, most ITP megakaryocytes show ultrastructural features of (para-) apoptosis, probably due to action of factors present in ITP plasma. |
| Databáze: | OpenAIRE |
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