PM2.5 Increases Systemic Inflammatory Cells and Associated Disease Risks by Inducing NRF2-Dependent Myeloid-Biased Hematopoiesis in Adult Male Mice

Pulmonary exposure to PM2.5 induces NRF2-dependentstress hematopoiesis in the lungs and BM and produces related healthoutcomes. AlthoughPM(2.5) (fine particles with aerodynamic diameter<2.5 mu m) exposure shows the potential to impact normal hematopoiesis,the detailed alterations in systemic hematopoiesis and the underlyingmechanisms remain unclear. For hematopoiesis under steady-state orstress conditions, nuclear factor erythroid 2-related factor 2 (NRF2)is essential for regulating hematopoietic processes to maintain bloodhomeostasis. Herein, we characterized changes in the populations ofhematopoietic stem progenitor cells and committed hematopoietic progenitorsin the lungs and bone marrow (BM) of wild-type and Nrf2 (-/-) C57BL/6J male mice. PM2.5-induced NRF2-dependent biased hematopoiesis toward myeloid lineagein the lungs and BM generates excessive numbers of various inflammatoryimmune cells, including neutrophils, monocytes, and platelets. Theincreased population of these immune cells in the lungs, BM, and peripheralblood has been associated with observed pulmonary fibrosis and highdisease risks in an NRF2-dependent manner. Therefore, although NRF2is a protective factor against stressors, upon PM2.5 exposure,NRF2 is involved in stress myelopoiesis and enhanced PM2.5 toxicity in pulmonary injury, even leading to systemic inflammation.

Automated summary

Pulmonary exposure to PM2.5 induces stress hematopoiesis dependent on NRF2 in the lungs and bone marrow, resulting in related health outcomes. The detailed alterations in systemic hematopoiesis and the underlying mechanisms under PM2.5 exposure are still unclear. NRF2 is essential for regulating hematopoiesis under steady-state or stress conditions, but upon PM2.5 exposure, it is involved in stress myelopoiesis and enhanced PM2.5 toxicity, leading to systemic inflammation.