Differential Impacts of Components of Particulate Matter on Epithelial Cell Toxicity and Immune Responses

Poor air quality, and particularly particulate matter (PM), is detrimental to health, contributing to chronic inflammatory conditions and worsening the outcomes to infections. PM has major impacts on barrier tissues including the lungs, gut, and skin. These tissues are lined by epithelial cells that can initiate and contribute to immune responses, but we still do not fully understand how they respond to PM. Furthermore, PM is multifactorial, and which components may be the most triggering for immune responses are not known. We evaluated the impact of a range of PM components including transition metals and components of diesel exhaust particulates (DEP) on lung-, gut-, and skin-derived epithelial cells. Differences in toxicity were observed between components, with the polyaromatic hydrocarbon 1, 2-naphthoquinone extremely toxic at concentrations of 100 μg/mL, contrasting with 2-nitrofluorenone and 2-methyl-4-nitrophenol. At lower nonlethal concentrations, 1, 2-naphthoquinone promoted epithelial cell production of the chemokines CXCL1 and CXCL2 that are associated with neutrophil recruitment, contrasting with other pollutants evaluated. Furthermore, 1, 2-naphthoquinone caused broad transcriptional changes in the lung epithelial cells. These results highlight the potential dangers of discrete components of PM such as 1, 2-naphthoquinone on epithelial function, indicating the potential to alter the immune landscape in the lung.