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Updated: Aug 24, 2026
Reprograming Model of Human Monocyte-derived Macrophages for In-vitro Assays
Published on: April 18, 2025
Reprogramming of human postmitotic neutrophils into macrophages by growth factors
Hiroto Araki1, Naoyuki Katayama, Yoshihiro Yamashita
1Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.
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.
Insights
Postmitotic neutrophils can transform into macrophages. This study demonstrates a novel neutrophil-to-macrophage lineage switch in human cells, expanding our understanding of hematopoiesis.
Area of Science:
- Immunology
- Cell Biology
- Hematopoiesis
Background:
- Postmitotic neutrophils are traditionally considered terminally differentiated cells.
- Existing knowledge suggests neutrophils exclusively differentiate into polymorphonuclear neutrophils.
Purpose of the Study:
- To investigate the potential for lineage plasticity in human postmitotic neutrophils.
- To determine if neutrophils can differentiate into other myeloid cell types, specifically macrophages.
Main Methods:
- Culture of CD15+CD14- neutrophils (band neutrophils) with a cocktail of cytokines (GM-CSF, TNF-α, IFN-γ, IL-4) followed by M-CSF.
- Morphological, cytochemical, and phenotypic analysis of resultant cells.
- Gene expression profiling (microarray) and functional assays (phagocytosis).
- Assessment for progenitor cell contamination using Ki-67, BrdU incorporation, and dye labeling.
Main Results:
- Cultured neutrophils acquired macrophage characteristics, including morphology, cytochemistry, and phenotype.
- Downregulation of neutrophil markers (MPO, specific esterase, lactoferrin) and upregulation of macrophage markers (non-specific esterase, M-CSF receptor, mannose receptor, HLA-DR).
- Gene expression analysis confirmed neutrophil-to-macrophage lineage conversion.
- Derived macrophages exhibited phagocytic function.
- Evidence ruled out contamination by macrophage progenitors.
Conclusions:
- Postmitotic human neutrophils can undergo a lineage switch to become macrophages in response to specific cytokine stimulation.
- This represents a previously unrecognized differentiation pathway in human hematopoiesis.
- Neutrophil plasticity offers new insights into immune cell generation and function.
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