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Reactive Oxygen Species–Producing Myeloid Cells Act as a Bone Marrow Niche for Sterile Inflammation–Induced Reactive Granulopoiesis
- Source :
- The Journal of Immunology. 198:2854-2864
- Publication Year :
- 2017
- Publisher :
- The American Association of Immunologists, 2017.
-
Abstract
- Both microbial infection and sterile inflammation augment bone marrow (BM) neutrophil production, but whether the induced accelerated granulopoiesis is mediated by a common pathway and the nature of such a pathway are poorly defined. We recently established that BM myeloid cell–derived reactive oxygen species (ROS) externally regulate myeloid progenitor proliferation and differentiation in bacteria-elicited emergency granulopoiesis. In this article, we show that BM ROS levels are also elevated during sterile inflammation. Similar to in microbial infection, ROS were mainly generated by the phagocytic NADPH oxidase in Gr1+ myeloid cells. The myeloid cells and their ROS were uniformly distributed in the BM when visualized by multiphoton intravital microscopy, and ROS production was both required and sufficient for sterile inflammation–elicited reactive granulopoiesis. Elevated granulopoiesis was mediated by ROS-induced phosphatase and tensin homolog oxidation and deactivation, leading to upregulated PtdIns(3,4,5)P3 signaling and increased progenitor cell proliferation. Collectively, these results demonstrate that, although infection-induced emergency granulopoiesis and sterile inflammation–elicited reactive granulopoiesis are triggered by different stimuli and are mediated by distinct upstream signals, the pathways converge to NADPH oxidase–dependent ROS production by BM myeloid cells. Thus, BM Gr1+ myeloid cells represent a key hematopoietic niche that supports accelerated granulopoiesis in infective and sterile inflammation. This niche may be an excellent target in various immune-mediated pathologies or immune reconstitution after BM transplantation.
- Subjects :
- Male
0301 basic medicine
Myeloid
Blotting, Western
Immunology
Cell Separation
Granulopoiesis
Article
Mice
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Immunology and Allergy
Granulocyte Precursor Cells
Myeloid Cells
Stem Cell Niche
Progenitor cell
Inflammation
chemistry.chemical_classification
Reactive oxygen species
Microscopy, Confocal
NADPH oxidase
biology
Chemistry
Cell Differentiation
Flow Cytometry
Mice, Mutant Strains
Hematopoiesis
Cell biology
Mice, Inbred C57BL
Transplantation
Disease Models, Animal
Haematopoiesis
030104 developmental biology
medicine.anatomical_structure
biology.protein
Bone marrow
Reactive Oxygen Species
Granulocytes
030215 immunology
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 198
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....b446b14f200e4bb0d2dd3b84ba1060d9