MECHANISM OF SILICA- AND TITANIUM DIOXIDE-INDUCED CYTOTOXICITY IN ALVEOLAR MACROPHAGES

Abstract

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