Review of in vitro studies evaluating respiratory toxicity of aerosols: impact of cell types, chemical composition, and atmospheric processing

In recent decades, several cell-based and acellular methods have been developed to evaluate ambient particulate matter (PM) toxicity. Although cell-based methods provide a more comprehensive assessment of PM toxicity, their results are difficult to comprehend due to the diversity in cellular endpoints, cell types, and assays and the interference of PM chemical components with some of the assays' techniques. In this review, we attempt to clarify some of these issues. We first discuss the morphological and immunological differences among various macrophage and epithelial cells, belonging to the respiratory systems of human and murine species, used in the in vitro studies evaluating PM toxicity. Then, we review the current state of knowledge on the role of different PM chemical components and the relevance of atmospheric processing and aging of aerosols in the respiratory toxicity of PM. Our review demonstrates the need to adopt more physiologically relevant cellular models such as epithelial (or endothelial) cells instead of macrophages for oxidative stress measurement. We suggest limiting macrophages for investigating other cellular responses (e.g., phagocytosis, inflammation, and DNA damage). Unlike monocultures (of macrophages and epithelial cells), which are generally used to study the direct effects of PM on a given cell type, the use of co-culture systems should be encouraged to investigate a more comprehensive effect of PM in the presence of other cells. Our review has identified two major groups of toxic PM chemical species from the existing literature, i.e., metals (Fe, Cu, Mn, Cr, Ni, and Zn) and organic compounds (PAHs, ketones, aliphatic and chlorinated hydrocarbons, and quinones). However, the relative toxicities of these species are still a matter of debate. Finally, the results of the existing studies investigating the effect of aging on PM toxicity are ambiguous, with varying results due to different cell types, different aging conditions, and the presence/absence of specific oxidants. More systematic studies are necessary to understand the role of different SOA precursors, interactions between different PM components, and aging conditions in the overall toxicity of PM. We anticipate that our review will guide future investigations by helping researchers choose appropriate cell models, resulting in a more meaningful interpretation of cell-based assays and thus ultimately leading to a better understanding of the health effects of PM exposure.