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Blood, 15 August 2007, Vol. 110, No. 4, pp. 1153-1160. Prepublished online as a Blood First Edition Paper on May 10, 2007; DOI 10.1182/blood-2007-01-067116. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-01-067116v1 110/4/1153    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 Lambert, M. P. Articles by Poncz, M. Search for Related Content PubMed PubMed Citation Articles by Lambert, M. P. Articles by Poncz, M. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Chemokines, Cytokines, and Interleukins Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Platelet factor 4 is a negative autocrine in vivo regulator of megakaryopoiesis: clinical and therapeutic implications Michele P. Lambert1,2, Lubica Rauova1,3, Matthew Bailey4, Martha C. Sola-Visner4, M. Anna Kowalska1,5, and Mortimer Poncz1,2 1 Department of Pediatrics, Children's Hospital of Philadelphia, PA; 2 Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia; 3 National Institute for Rheumatic Diseases, Piestany, Slovakia; 4 Department of Pediatrics, Drexel University College of Medicine, Philadelphia, PA; 5 Center for Medical Biology, Polish Academy of Science, Lodz, Poland Platelet factor 4 (PF4) is a negative regulator of megakaryopoiesis in vitro. We have now examined whether PF4 regulates megakaryopoiesis in vivo by studying PF4 knockout mice and transgenic mice that overexpress human (h) PF4. Steady-state platelet count and thrombocrit in these animals was inversely related to platelet PF4 content. Growth of megakaryocyte colonies was also inversely related to platelet PF4 content. Function-blocking anti-PF4 antibody reversed this inhibition of megakaryocyte colony growth, indicating the importance of local PF4 released from developing megakaryocytes. The effect of megakaryocyte damage and release of PF4 on 5-fluorouracil–induced marrow failure was then examined. Severity of thrombocytopenia and time to recovery of platelet counts were inversely related to initial PF4 content. Recovery was faster and more extensive, especially in PF4-overexpressing mice, after treatment with anti-PF4 blocking antibodies, suggesting a means to limit the duration of such a chemotherapy-induced thrombocytopenia, especially in individuals with high endogenous levels of PF4. We found that approximately 8% of 250 healthy adults have elevated (> 2 times average) platelet PF4 content. These individuals with high levels of platelet PF4 may be especially sensitive to developing thrombocytopenia after bone marrow injury and may benefit from approaches that block the effects of released PF4. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: What for platelet factor 4? Andrew D. Leavitt Blood 2007 110: 1090. [Full Text] [PDF] This article has been cited by other articles: J. J. Bernard, K. E. Seweryniak, A. D. Koniski, S. L. Spinelli, N. Blumberg, C. W. Francis, M. B. Taubman, J. Palis, and R. P. Phipps Foxp3 Regulates Megakaryopoiesis and Platelet Function Arterioscler Thromb Vasc Biol, November 1, 2009; 29(11): 1874 - 1882. [Abstract] [Full Text] [PDF] M. P. Lambert, Y. Wang, K. H. Bdeir, Y. Nguyen, M. A. Kowalska, and M. Poncz Platelet factor 4 regulates megakaryopoiesis through low-density lipoprotein receptor-related protein 1 (LRP1) on megakaryocytes Blood, September 10, 2009; 114(11): 2290 - 2298. [Abstract] [Full Text] [PDF] D. J. Hilton, B. T. Kile, and W. S. Alexander Mutational inhibition of c-Myb or p300 ameliorates treatment-induced thrombocytopenia Blood, May 28, 2009; 113(22): 5599 - 5604. [Abstract] [Full Text] [PDF] T. E. Warkentin, J.-A. I. Sheppard, J. C. Moore, R. J. Cook, and J. G. Kelton Studies of the immune response in heparin-induced thrombocytopenia Blood, May 14, 2009; 113(20): 4963 - 4969. [Abstract] [Full Text] [PDF] K. A. Tanaka, N. S. Key, and J. H. Levy Blood Coagulation: Hemostasis and Thrombin Regulation Anesth. Analg., May 1, 2009; 108(5): 1433 - 1446. [Abstract] [Full Text] [PDF] C. A. Gleissner, P. von Hundelshausen, and K. Ley Platelet Chemokines in Vascular Disease Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1920 - 1927. [Abstract] [Full Text] [PDF] J. G. Kelton and T. E. Warkentin Heparin-induced thrombocytopenia: a historical perspective Blood, October 1, 2008; 112(7): 2607 - 2616. [Full Text] [PDF] S. Suvarna, B. Espinasse, R. Qi, R. Lubica, M. Poncz, D. B. Cines, M. R. Wiesner, and G. M. Arepally Determinants of PF4/heparin immunogenicity Blood, December 15, 2007; 110(13): 4253 - 4260. [Abstract] [Full Text] [PDF]

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