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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.
HEMATOPOIESIS Reprogramming of human postmitotic neutrophils into macrophages by growth factorsFrom the Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan; the Division of Functional Genomics, Jichi Medical School, Kawachi-cho, Japan; and the Blood Transfusion Service, Mie University Hospital, Tsu, Japan.
It is generally recognized that postmitotic neutrophils give rise to polymorphonuclear neutrophils alone. We obtained evidence for a lineage switch of human postmitotic 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-
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| Copyright © 2004 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
, interferon-
, and interleukin-4, and subsequently with macrophage colony-stimulating factor alone, the resultant cells had morphologic, cytochemical, and phenotypic features of macrophages. In contrast to the starting population, they were negative for myeloperoxidase, specific esterase, and lactoferrin, and they up-regulated nonspecific 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 3 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, postmitotic neutrophils can become macrophages. This may represent another differentiation pathway toward macrophages in human postnatal hematopoiesis. (Blood. 2004;103:2973-2980) 
