title: Myeloid cell-derived reactive oxygen species externally regulate the proliferation of myeloid progenitors in emergency granulopoiesis.
abstract: The cellular mechanisms controlling infection-induced emergency granulopoiesis are poorly defined. Here we found that reactive oxygen species (ROS) concentrations in the bone marrow (BM) were elevated during acute infection in a phagocytic NADPH oxidase-dependent manner in myeloid cells. Gr1(+) myeloid cells were uniformly distributed in the BM, and all c-kit(+) progenitor cells were adjacent to Gr1(+) myeloid cells. Inflammation-induced ROS production in the BM played a critical role in myeloid progenitor expansion during emergency granulopoiesis. ROS elicited oxidation and deactivation of phosphatase and tensin homolog (PTEN), resulting in upregulation of PtdIns(3,4,5)P3 signaling in BM myeloid progenitors. We further revealed that BM myeloid cell-produced ROS stimulated proliferation of myeloid progenitors via a paracrine mechanism. Taken together, our results establish that phagocytic NADPH oxidase-mediated ROS production by BM myeloid cells plays a critical role in mediating emergency granulopoiesis during acute infection.
authors.affiliation: Department of Pathology, Harvard Medical School; Department of Lab Medicine, Children's Hospital Boston; Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Kwak
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Pathology, Harvard Medical School; Department of Lab Medicine, Children's Hospital Boston; Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.
authors.forename: Besnik
authors.initials: B
authors.lastname: Bajrami
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, China.
authors.forename: Yuanfu
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathology, Harvard Medical School; Department of Lab Medicine, Children's Hospital Boston; Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.
authors.forename: Shin-Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Experimental Hematology, University Hospital Zurich, Schmelzbergstrasse 12, PATH G37, 8091 Zurich, Switzerland.
authors.forename: César
authors.initials: C
authors.lastname: Nombela-Arrieta
authors.affiliation: Department of Pathology, Harvard Medical School; Department of Lab Medicine, Children's Hospital Boston; Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.
authors.forename: Subhanjan
authors.initials: S
authors.lastname: Mondal
authors.affiliation: Department of Pathology, Harvard Medical School; Department of Lab Medicine, Children's Hospital Boston; Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Chai
authors.affiliation: Department of Pathology, Harvard Medical School; Department of Lab Medicine, Children's Hospital Boston; Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.
authors.forename: Leslie E
authors.initials: LE
authors.lastname: Silberstein
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.affiliation: Department of Pathology, Harvard Medical School; Department of Lab Medicine, Children's Hospital Boston; Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA. Electronic address: hongbo.luo@childrens.harvard.edu.
authors.forename: Hongbo R
authors.initials: HR
authors.lastname: Luo
mesh_terms: D000208:Acute Disease; D000818:Animals; D001853:Bone Marrow / Q000382:microbiology / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology*; D006098:Granulocytes / Q000502:physiology*; D006410:Hematopoiesis / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000502:physiology*; D023461:Myeloid Progenitor Cells / Q000502:physiology*; D019255:NADPH Oxidases / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019899:Paracrine Communication; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D018129:Phosphatidylinositol Phosphates; D017382:Reactive Oxygen Species; C060974:phosphatidylinositol 3,4,5-triphosphate; D019255:NADPH Oxidases; D051059:PTEN Phosphohydrolase