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

Abstract

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 (O₃), a highly reactive oxidant gas, respiratory health hazard, and common environmental air pollutant at ground level. The respiratory health effects due to O₃ 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 O₃-exposed respiratory tract, with emphasis on mouse model-based toxicological studies. Critical findings from 39 studies containing the words O₃, 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 O₃-induced lung diseases. Moreover, a comprehensive list of currently known macrophage-specific roles in O₃-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 O₃.

Keywords:

• Ozone
• macrophages
• airspaces
• lung
• epithelial lining fluid

Acknowledgments

The authors are grateful for the funding provided by the National Institute of Environmental Health Sciences (NIEHS) Grant R01ES030125. The authors gratefully acknowledge the extensive critiques suggested by the three reviewers that were selected by the Editor and presented anonymously to the authors. The authors also gratefully acknowledge valuable feedback received from Dr. Roger O McClellan. These critiques were extremely helpful in revising the manuscript.

Declaration of interest

The employment affiliation of both the authors is included in the cover page. This work was funded by National Institute of Environmental Health Sciences (NIEHS). Authors involved in the preparation of this manuscript did not receive any compensation from any source and declare that they have no potential conflict of interest. The preparation of this review was conducted during normal course of author’s employment. Both the authors conducted literature search, planned the outline of the manuscript, wrote, and edited the manuscript. The authors have the sole responsibility for the writing and content of the manuscript. None of the authors have been previously involved in any litigation, advocacy or regulatory activities related to the contents of this review.

The authors declare that there is no conflict of interest regarding the publication of this article.