Mechanism of silica- and titanium dioxide-induced cytotoxicity in alveolarmacrophages

Particles can cause cytotoxicity in pulmonary alveolar macrophages (AM). Se veral mechanisms to explain this cytotoxicity have been suggested. However, the exact mechanism of particle-induced cytotoxicity in AIM remains to be established. Silica and TiO2 produced a concentration-dependent cytotoxicit y as evidenced by loss of cell viability and fall in ATP levels. While sili ca induced a greater cytotoxicity, TiO2 produced a higher reduction in ATP levels. Silica increased the release of LDH, but TiO2 did not affect enzyma tic release. TiO2 suppressed succinate-triggered oxygen consumption, wherea s silica did not markedly change the effect of succinate on oxygen consumpt ion. Polyinosinic acid (Pl), a ligand of the scavenger receptor, inhibited the TiO2-induced fall in ATP content, but could not prevent the effect of s ilica on cellular ATP content. Data suggest that silica and TiO2 can induce cytotoxicity in AM, probably through different mechanisms.