An Italian Study of PM 0.5 Toxicity: In Vitro Investigation of Cytotoxicity, Oxidative Stress, Intercellular Communication, and Extracellular Matrix Metalloproteases

Particulate matter (PM), mainly PM0.5, represents a significant concern for human health, particularly relating to lung homeostasis, and more research is required to ascertain its tissue tropism and the molecular pathways involved. In this study, we first focus on classical in vitro toxicological endpoints (cytotoxicity and cell growth) in human bronchial and alveolar epithelial cell lines mimicking the two pulmonary target tissues. Air samples were collected in five Italian cities (Brescia, Lecce, Perugia, Pisa, Turin) during winter and spring. To better decipher the PM0.5 effects on pulmonary cells, a further winter sampling was performed in Brescia, and studies were extended to assess tumour promotion, oxidative stress, and the activity of Matrix metalloproteases (MMP). The results confirmed that the effect of air pollution is linked to the seasons (winter is usually more cytotoxic than spring) and is correlated with the peculiar characteristics of the cities studied (meteoclimatic conditions, economic/anthropogenic activities). Alveolar cells were often less sensitive than bronchial cells. All PM samples from Brescia inhibited intercellular communication mediated by gap junctions (GJIC), increased the total content in glutathione, and decreased the reduced form of glutathione, whereas the Reactive Oxygen Species (ROS) content was almost constant. Long-term treatments at higher doses of PM decreased MMP2 and MMP9 activity. Taken together, the results confirmed that PM is cytotoxic and can potentially act as tumour promoters, but the mechanisms involved in oxidative stress and lung homeostasis are dose- and time-dependent and quite complex.