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Blood, 15 April 2004, Vol. 103, No. 8, pp. 2973-2980. Prepublished online as a Blood First Edition Paper on December 30, 2003; DOI 10.1182/blood-2003-08-2742. This Article Full Text (PDF) All Versions of this Article: 2003-08-2742v1 103/8/2973    most recent Alert me when this article is cited Alert me if a correction is posted 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 Araki, H. Articles by Shiku, H. Search for Related Content PubMed PubMed Citation Articles by Araki, H. Articles by Shiku, H. Social Bookmarking                   What's this? Submitted August 12, 2003 Accepted December 18, 2003 Reprogramming of human post-mitotic neutrophils into macrophages by growth factors Hiroto Araki, Naoyuki Katayama*, Yoshihiro Yamashita, Hiroyuki Mano, Atsushi Fujieda, Eiji Usui, Hidetsugu Mitani, Kohshi Ohishi, Kazuhiro Nishii, Masahiro Masuya, Nobuyuki Minami, Tsutomu Nobori, and Hiroshi Shiku The Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie, Japan Division of Functional Genomics, Jichi Medical School, Kawachi-gun, Tochigi, Japan Blood Transfusion Service, Mie University Hospital, Tsu, Mie, Japan * Corresponding author; email: n-kata{at}clin.medic.mie-u.ac.jp. It is generally recognized that post-mitotic neutrophils give rise to polymorphonuclear neutrophils alone. We obtained evidence for a lineage switch of human post-mitotic neutrophils into macrophages in culture. When the CD15+CD14- cell population, which predominantly consists of band neutrophils, was cultured with granulocyte/macrophage colony-stimulating factor, tumor necrosis factor-, interferon-, and interleukin-4, and subsequently with macrophage colony-stimulating factor alone, the resulting cells had morphological, cytochemical, and phenotypic features of macrophages; in contrast to the starting population, they were negative for myeloperoxidase, specific esterase, and lactoferrin and also upregulated non-specific esterase activity and the expression of macrophage colony-stimulating factor receptor, mannose receptor, and HLA-DR. CD15+CD14- cells proceeded to macrophages through the CD15-CD14- cell population. Microarray analysis of gene expression also disclosed the lineage conversion from neutrophils to macrophages. Macrophages derived from CD15+CD14- neutrophils had phagocytic function. Data obtained using three different techniques, including Ki-67 staining, bromodeoxyuridine incorporation, and cytoplasmic dye labeling, together with the yield of cells, indicated that the generation of macrophages from CD15+CD14- neutrophils did not result from a contamination of progenitors for macrophages. Our data show that in response to cytokines, post-mitotic neutrophils can become macrophages. This may represent another differentiation pathway toward macrophages in human postnatal hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Mandruzzato, S. Solito, E. Falisi, S. Francescato, V. Chiarion-Sileni, S. Mocellin, A. Zanon, C. R. Rossi, D. Nitti, V. Bronte, et al. IL4R{alpha}+ Myeloid-Derived Suppressor Cell Expansion in Cancer Patients J. Immunol., May 15, 2009; 182(10): 6562 - 6568. [Abstract] [Full Text] [PDF] A. S. Cowburn, A. M. Condliffe, N. Farahi, C. Summers, and E. R. Chilvers Advances in Neutrophil Biology: Clinical Implications Chest, September 1, 2008; 134(3): 606 - 612. [Abstract] [Full Text] [PDF] R. T. Sasmono, A. Ehrnsperger, S. L. Cronau, T. Ravasi, R. Kandane, M. J. Hickey, A. D. Cook, S. R. Himes, J. A. Hamilton, and D. A. Hume Mouse neutrophilic granulocytes express mRNA encoding the macrophage colony-stimulating factor receptor (CSF-1R) as well as many other macrophage-specific transcripts and can transdifferentiate into macrophages in vitro in response to CSF-1 J. Leukoc. Biol., July 1, 2007; 82(1): 111 - 123. [Abstract] [Full Text] [PDF] H. Araki, K. Yoshinaga, P. Boccuni, Y. Zhao, R. Hoffman, and N. Mahmud Chromatin-modifying agents permit human hematopoietic stem cells to undergo multiple cell divisions while retaining their repopulating potential Blood, April 15, 2007; 109(8): 3570 - 3578. [Abstract] [Full Text] [PDF] N. Hoshino, N. Katayama, T. Shibasaki, K. Ohishi, J. Nishioka, M. Masuya, Y. Miyahara, M. Hayashida, D. Shimomura, T. Kato, et al. A novel role for Notch ligand Delta-1 as a regulator of human Langerhans cell development from blood monocytes J. Leukoc. Biol., October 1, 2005; 78(4): 921 - 929. [Abstract] [Full Text] [PDF]

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