An Interspecies Comparison of the Phagocytosis and Dissolution of²⁴¹AmO₂Particles by Rat, Dog and Monkey Alveolar Macrophagesin 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.

Intracellular Particle Dissolution in Alveolar Macrophages

“…range of 5 (45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60), it is plausible to conclude that the intracellular mechanism of particle dissolution is controlled by these two parameters. However, at this moment we cannot exclude other mechanisms of IPD resulting from proteolytic enzymes, oxygen radicals, chelators, precipitators, etc., that are contained in the phagolysosomal plasma (20).…”

“…In another study, dissolution of polydisperse, radioactive 244AmO2 particles was determined in cultured AM obtained from monkeys, dogs, and rats (46,47). Dissolution in the cell culture system increased linearly to 10% of the initial particle amount after 3 days of incubation, whereas dissolution ofthe AmO2 particles in the culture medium only was constant at 1% ofthe initial particle amount.…”

The impact of nanomaterial characteristics on inhalation toxicity

“…These parameters, e.g., solvent, pH, possible adsorptions on the surface, and already existing constituent concentration, vary between species, organs and cells. 163,180,181 For instance, varying macrophage-mediated dissolution rates for different species were found in a comparison between humans and canines for cobalt oxide (Co 3 O 4 ) particles, 182 but similar capacities were found in humans and rabbits with regard to manganese oxide (Mn 2 O 3 ). 183 For Incontaining ENMs, a difference between cell types could also be observed as only macrophages, but not epithelial cells, exhibited more efficient dissolution and strong toxicity after ENM internalization.…”

Isotope Tracers To Study the Environmental Fate and Bioaccumulation of Metal-Containing Engineered Nanoparticles: Techniques and Applications

“…An interspecies comparison of the phagocytosis and dissolution of 241 AmO 2 particles by rat, dog, and monkey alveolar macrophages showed that dog and monkey macrophages took up 241 AmO 2 particles at similar rates, whereas rat macrophages phagocytosed only 60% of the amount phagocytosed by dog and monkey macrophages. 46 The three macrophage species dissolved 241 AmO 2 particles at similar rates (8−10% by 72 h), implying that the dissolution of 241 AmO 2 particles by alveolar macrophages might be species-independent. The intracellular dissolution of different-sized 57 Co 3 O 4 particles by human and canine alveolar macrophages showed that 57 Co 3 O 4 particles were relatively insoluble in extracellular medium, and smaller-sized 57 Co 3 O 4 particles had a faster intracellular dissolution rate than larger particles.…”

“…Most metals in MENPs have at least two stable isotopes, except for Au and Ce (Table 1). Usually, several isotopes are commercially available for one metal (e.g., 46 Ti, 47 Ti, 48 Ti, 49 Ti, 50 Ti). Generally, tracing MENPs with highly enriched isotopes of low natural abundance provide the best sensitivity.…”