Reprogramming of human postmitotic neutrophils into macrophages by growth factors.
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.
Araki
Hiroto
H
Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.
Katayama
Naoyuki
N
Yamashita
Yoshihiro
Y
Mano
Hiroyuki
H
Fujieda
Atsushi
A
Usui
Eiji
E
Mitani
Hidetsugu
H
Ohishi
Kohshi
K
Nishii
Kazuhiro
K
Masuya
Masahiro
M
Minami
Nobuyuki
N
Nobori
Tsutomu
T
Shiku
Hiroshi
H
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
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