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

Abstract

Although PM_2.5 (fine particles with aerodynamic diameter <2.5 μm) exposure shows the potential to impact normal hematopoiesis, the detailed alterations in systemic hematopoiesis and the underlying mechanisms remain unclear. For hematopoiesis under steady-state or stress conditions, nuclear factor erythroid 2-related factor 2 (NRF2) is essential for regulating hematopoietic processes to maintain blood homeostasis. Herein, we characterized changes in the populations of hematopoietic stem progenitor cells and committed hematopoietic progenitors in the lungs and bone marrow (BM) of wild-type and Nrf2^–/– C57BL/6J male mice. PM_2.5-induced NRF2-dependent biased hematopoiesis toward myeloid lineage in the lungs and BM generates excessive numbers of various inflammatory immune cells, including neutrophils, monocytes, and platelets. The increased population of these immune cells in the lungs, BM, and peripheral blood has been associated with observed pulmonary fibrosis and high disease risks in an NRF2-dependent manner. Therefore, although NRF2 is a protective factor against stressors, upon PM_2.5 exposure, NRF2 is involved in stress myelopoiesis and enhanced PM_2.5 toxicity in pulmonary injury, even leading to systemic inflammation.