Effects of PM2.5 exposure on hematopoiesis and coupled immune disorder in adult male mice

Abstract

Fine particulate matter, namely PM_2.5, increases the risk of morbidity and mortality in various systems, including the hematopoietic and immune systems. However, there is limited experimental evidence supporting the association between PM_2.5 exposure and hematopoietic outcomes as most studies focus on epidemiological data. In this study, adult male mice were exposed to PM_2.5 for a long time to investigate hematopoietic toxicity. There were significant increases in red blood cells (RBC), hemoglobin (HGB), and white blood cells (WBC) in peripheral blood after 5-month real-environmental PM_2.5 exposure, indicating elevated circulatory inflammation and potential hematopoietic abnormality. Moreover, we observed abnormal proliferation and differentiation of hematopoietic stem and progenitor cells (HSPCs), along with altered mRNA levels of hematopoietic genes and increased proinflammatory factors in the bone marrow (BM). Transcriptomic analysis of BM cells suggested that PM_2.5 exposure activated immune responses associated with lymphocytes. Then, PM_2.5 exposure via intratracheal instillation was performed for 8 weeks to verify the toxic effect. The results of the complete blood count were similar to those of real-environmental exposure, with drastic changes in the number and function of HSPCs, as well as mRNA levels of the hematopoietic genes and increased inflammatory factors in the BM being detected. Furthermore, lymphocyte subsets changed significantly in the BM and spleen, confirming immune disorder following PM_2.5 exposure. In conclusion, PM_2.5 interfered with the process of BM hematopoiesis by triggering inflammation and leading to immune disorder. Our study provided experimental evidence for the hematopoietic toxicity of PM_2.5 and highlighted the significance of reducing air pollution.