Variations in the expression and function of SARS-CoV-2 entry molecules induced by exposure to nano- and microparticles

• Effects of particles on SARS-CoV-2 entry molecules were evaluated. • Titanium dioxide exposure upregulated ACE2 and TMPRSS2 expression and function. • Asian sand dust exposure promoted only the function of TMPRSS2. • Serine protease inhibitors suppressed TMPRSS2 activity promoted by Asian sand dust. Several epidemiological studies have reported an association between the onset and severity of coronavirus disease 2019 and exposure to particulate matter (PM). However, the detailed molecular mechanisms remain unclear. In this study, we evaluated variations in the expression and function of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), the entry molecules of SARS-CoV-2, when type II alveolar epithelial cells were exposed to titanium dioxide particles (TiO 2 ), diesel exhaust particles (DEP), and Asian sand dust (ASD). The results showed that TiO 2 exposure increased the expression and activity of ACE2 and TMPRSS2 on the exposed cells, while ASD exposure only increased the activity of TMPRSS2. Furthermore, we found that serine protease inhibitors such as nafamostat can regulate TMPRSS2 activity promoted by PM exposure. Our results provide experimental evidence that exposure to PM with specific properties may enhance intracellular entry of SARS-CoV-2.