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Blood, 1 December 2004, Vol. 104, No. 12, pp. 3573-3580. Prepublished online as a Blood First Edition Paper on August 3, 2004; DOI 10.1182/blood-2004-01-0193. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-01-0193v1 104/12/3573    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Centurione, L. Articles by Migliaccio, A. R. Search for Related Content PubMed PubMed Citation Articles by Centurione, L. Articles by Migliaccio, A. R. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Phagocytes Apoptosis Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Increased and pathologic emperipolesis of neutrophils within megakaryocytes associated with marrow fibrosis in GATA-1low mice Lucia Centurione, Angela Di Baldassarre, Maria Zingariello, Domenico Bosco, Valentina Gatta, Rosa Alba Rana, Vincenzo Langella, Antonio Di Virgilio, Alessandro M. Vannucchi, and Anna Rita Migliaccio From the Departments of Biomorphology and Biomedical Sciences, University "G. D'Annunzio," Chieti, Italy; CNR Institute for Organ Transplantation and Immunocytology, Chieti, Italy; Experimental Zoo-prophylactic Institute "G. Caporale," Teramo, Italy; Department of Hematology University of Firenze, Florence, Italy; and Laboratories of Security and Quality of Animal Experimentation and of Clinical Biochemistry, Istituto Superiore Sanità, Rome, Italy. Deletion of megakaryocytic-specific regulatory sequences of GATA-1 (Gata1tm2Sho or GATA-1low mutation) results in severe thrombocytopenia, because of defective thrombocytopoiesis, and myelofibrosis. As documented here, the GATA-1low mutation blocks megakaryocytic maturation between stage I and II, resulting in accumulation of defective megakaryocytes (MKs) in the tissues of GATA-1low mice. The block in maturation includes failure to properly organize granules because von Willebrand factor is barely detectable in mutant MKs, and P-selectin, although normally expressed, is found frequently associated with the demarcation membrane system (DMS) instead of within granules. Conversely, both von Willebrand factor and P-selectin are barely detectable in GATA-1low platelets. Mutant MKs are surrounded by numerous myeloperoxidase-positive neutrophils, some of which appear in the process to establish contact with MKs by fusing their membrane with those of the DMS. As a result, 16% (in spleen) to 34% (in marrow) of GATA-1low MKs contain 1 to 3 neutrophils embedded in a vacuolated cytoplasm. The neutrophil-embedded GATA-1low MKs have morphologic features (high electron density and negativity to TUNEL staining) compatible with those of cells dying from para-apoptosis. We suggest that such an increased and pathologic neutrophil emperipolesis may represent one of the mechanisms leading to myelofibrosis by releasing fibrogenic MK cytokines and neutrophil proteases in the microenvironment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Zingariello, D. Bosco, B. Ghinassi, R. A. Rana, F. A. Manzoli, and A. R. Migliaccio Peripolesis of Fibroblasts around Megakaryocytes: A New Pathological Cellular Interaction Leading to Megakaryocyte Para-Apoptosis in Gata1low Mice. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 3592 - 3592. [Abstract] [PDF] A. R. Migliaccio and S. Philipsen Reflections on the European Union Eurythron Network Meeting "Molecular Control of Erythropoiesis," September 22-23, 2005, Istituto Superiore Di Sanita, Rome, Italy Stem Cells, November 1, 2006; 24(11): 2478 - 2482. [Abstract] [Full Text] [PDF] F. Martelli, B. Ghinassi, B. Panetta, E. Alfani, V. Gatta, A. Pancrazzi, C. Bogani, A. M. Vannucchi, F. Paoletti, G. Migliaccio, et al. Variegation of the phenotype induced by the Gata1low mutation in mice of different genetic backgrounds Blood, December 15, 2005; 106(13): 4102 - 4113. [Abstract] [Full Text] [PDF] A. Tefferi Pathogenesis of Myelofibrosis With Myeloid Metaplasia J. Clin. Oncol., November 20, 2005; 23(33): 8520 - 8530. [Abstract] [Full Text] [PDF] M. Zingariello, B. Ghinassi, R. A. Rana, L. R.N. Lorenzini, A. M. Vannucchi, F. Paoletti, and A. R. F. Migliaccio The Ultrastructure Features of the Advanced Stages of Fibrosis in GATA-1low Mice Are Similar to Those Found in Wound Healing. Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 3514 - 3514. [Abstract] A. M. Vannucchi, A. Pancrazzi, P. Guglielmelli, S. Di Lollo, C. Bogani, G. Baroni, L. Bianchi, A. R. Migliaccio, A. Bosi, and F. Paoletti Abnormalities of GATA-1 in Megakaryocytes from Patients with Idiopathic Myelofibrosis Am. J. Pathol., September 1, 2005; 167(3): 849 - 858. [Abstract] [Full Text] [PDF] M. Xu, E. Bruno, J. Chao, S. Huang, G. Finazzi, S. M. Fruchtman, U. Popat, J. T. Prchal, G. Barosi, R. Hoffman, et al. Constitutive mobilization of CD34+ cells into the peripheral blood in idiopathic myelofibrosis may be due to the action of a number of proteases Blood, June 1, 2005; 105(11): 4508 - 4515. [Abstract] [Full Text] [PDF] A. M. Vannucchi, L. Bianchi, F. Paoletti, A. Pancrazzi, E. Torre, M. Nishikawa, M. Zingariello, A. Di Baldassarre, R. A. Rana, R. Lorenzini, et al. A pathobiologic pathway linking thrombopoietin, GATA-1, and TGF-{beta}1 in the development of myelofibrosis Blood, May 1, 2005; 105(9): 3493 - 3501. [Abstract] [Full Text] [PDF]

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