Apoptosis of Pulmonary Neutrophils Induced by Low Dose Titanium Dioxide and Silica

Titanium dioxide (TiO2) is considered to be a non-fibrogenic dust and is widely used as a negative control in experimental studies. This may be because the initial inflammation caused by exposure resolves. Resolution of inflammation has been demonstrated to be related to neutrophil apoptosis. This study has examined the inflammatory reaction of the lung to intratracheal instillation of TiO2 and the occurrence of neutrophil apoptosis compared with the reaction to the same dose of silica. Specific pathogen-free Wistar rats were used. Forty rats were intratracheally instilled with either 2.5 mg/0.5 ml TiO2 or the same dose of Min-U-Sil 5 silica. At 1, 2, 3 and 5 days after instillation, five rats in each group were randomly selected, killed and lavaged. The lavage fluid obtained was used to prepare slides. Apoptotic neutrophils were counted and the proportion of apoptotic neutrophils to total neutrophils was calculated. A significant percentage of apoptotic neutrophils was detected in the TiO2-instilled group 1 day after instillation, peaking 3 days after exposure and disappearing at the 5 day point. In the silica-instilled group there was a delay in the emergence of apoptotic neutrophils. The inflammation in the silica-instilled group persisted, while that in the TiO2-instilled group resolved. It is concluded that intratracheal instillation of TiO2 can cause a rapid apoptotic reaction in alveolar neutrophils and neutrophil apoptosis may contribute to resolution of the TiO2-induced inflammation.