Myeloid Cell-Derived Reactive Oxygen Species Externally Regulate the Proliferation of Myeloid Progenitors in Emergency Granulopoiesis

Summary The cellular mechanisms controlling infection-induced emergency granulopoiesisare 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 myeloidcells. Gr1 + myeloidcells were uniformly distributed in the BM, and all c-kit + progenitorcells were adjacent to Gr1 + myeloidcells. Inflammation-induced ROS production in the BM played a critical role in myeloid progenitorexpansion during emergency granulopoiesis. ROS elicited oxidation and deactivation of phosphatase and tensinhomolog (PTEN), resulting in upregulation of PtdIns(3,4,5)P3 signaling in BM myeloid progenitors. We further revealed that BM myeloidcell-produced ROS stimulated proliferation of myeloid progenitorsvia a paracrine mechanism. Taken together, our results establish that phagocytic NADPH oxidase-mediated ROS production by BM myeloidcells plays a critical role in mediating emergency granulopoiesisduring acute infection.