Lung macrophages: current understanding of their roles in Ozone-induced lung diseases

Through the National Ambient Air Quality Standards (NAAQS), the Clean Air Act of the United States outlines acceptable levels of six different air pollutants considered harmful to humans and the environment. Included in this list is ozone (O), a highly reactive oxidant gas, respiratory health hazard, and common environmental air pollutant at ground level. The respiratory health effects due to O exposure are often associated with molecular and cellular perturbations in the respiratory tract. Periodic review of NAAQS requires comprehensive scientific evaluation of the public health effects of these pollutants, which is formulated through integrated science assessment (ISA) of the most policy-relevant scientific literature. This review focuses on the protective and pathogenic effects of macrophages in the O-exposed respiratory tract, with emphasis on mouse model-based toxicological studies. Critical findings from 39 studies containing the words O, macrophage, mice, and lung within the full text were assessed. While some of these studies highlight the presence of disease-relevant pathogenic macrophages in the airspaces, others emphasize a protective role for macrophages in O-induced lung diseases. Moreover, a comprehensive list of currently known macrophage-specific roles in O-induced lung diseases is included in this review and the significant knowledge gaps that still exist in the field are outlined. In conclusion, there is a vital need in this field for additional policy-relevant scientific information, including mechanistic studies to further define the role of macrophages in response to O