An Interspecies Comparison of the Phagocytosis and Dissolution of ²⁴¹AmO₂ Particles by Rat, Dog and Monkey Alveolar Macrophages in Vitro

Abstract

Because of the role that alveolar macrophages (PAM) play in the pulmonary clearance of inhaled particles via mechanical transport and dissolution, understanding the uptake and dissolution of particles by these cells might provide insight into the mechanisms of particle dissolution in lungs of various species and hence facilitate the extrapolation of animal data to humans. Therefore, experiments were conducted to study the phagocytosis and dissolution of ²⁴¹AmO₂ particles by rat, dog and monkey PAM in vitro. Rat, dog and monkey PAM were exposed for up to 72 h to 0·19, 0·93 or 4·6 kBq/ml ²⁴¹Am, after which cell viability was determined. The ²⁴¹Am concentration, 4·63 kBq/ml, was used for the phagocytosis and dissolution experiments. The phagocytosis and dissolution of ²⁴¹AmO₂ particles were followed up to 20 and 72 h, respectively. Dog and monkey PAM took up ²⁴¹AmO₂ particles at similar rates, whereas rat PAM phagocytosed only 60% of the amount phagocytosed by dog and monkey PAM at 20 h. The PAM of the three species dissolved ²⁴¹AmO₂ particles at similar rates; 8–10% was dissolved by 72 h. The results of the ²⁴¹AmO₂ uptake in vitro may reflect in vivo situations, where the differences in uptake seen in vitro would probably diminish at later times after exposure. The dissolution results imply that the dissolution of ²⁴¹AmO₂ particles by alveolar macrophages of the three species might be species-independent. This, at least, might be true for dog and monkey, where in vivo data have shown that ²⁴¹AmO₂ was translocated similarly in both species. Finally, the alveolar macrophage culture system provides a useful simulation to investigate uptake and dissolution of inhaled particles.