title: Reprogramming of human postmitotic neutrophils into macrophages by growth factors.
abstract: 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-alpha, interferon-gamma, 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.
authors.affiliation: Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Araki
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Katayama
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fujieda
authors.forename: Eiji
authors.initials: E
authors.lastname: Usui
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Mitani
authors.forename: Kohshi
authors.initials: K
authors.lastname: Ohishi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishii
authors.forename: Masahiro
authors.initials: M
authors.lastname: Masuya
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Minami
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nobori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiku
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000378:metabolism; D006410:Hematopoiesis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D016256:Lewis X Antigen / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D008938:Mitosis; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010587:Phagocytosis; D010641:Phenotype; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D006133:Growth Substances; D006684:HLA-DR Antigens; D016256:Lewis X Antigen; D018950:Lipopolysaccharide Receptors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor