Species Differences in Acute Pulmonary Responses to Inhaled Particles

Interspecies differences in alveolar macrophage (AM) function in vitro may account for differences in responses to inhaled particles in vivo. The current studies were undertaken to compare pulmonary clearance and inflammatory responses in rodents exposed to either carbonyl iron (CI) or silica particles. In the first set of studies, in vitro and in vivo pulmonary clearance responses were evaluated using two strains of rats and one strain each of mouse, hamster and guinea pig. in vitro studies showed that hamster AM had the highest phagocytic activity and that rat AM migrated best to complement-dependent chemotactic factors. Subsequently, groups of animals from each strain were exposed to aerosols of CI for 1 or 6 h at identical concentrations (100 mg m⁻³). Particle deposition patterns in the distal lung were nearly identical for all species, although increased numbers of CI particles were deposited on alveolar duct bifurcations of either rats or mice compared to hamsters and guinea pigs. Time-course studies showed that enhanced numbers of rat AM migrated to deposition sites and phagocytized particles, and this correlated with increased percentages of phagocytic macrophages recovered by lavage (P < 0.01). ACl-induced PMN inflammatory response was observed only in the mouse and this correlated with the lowest AM clearance rates in vivo and phagocytic rates in vitro. It was concluded from these studies that the rat model may be the most efficient rodent species for clearing inhaled iron particles. In another set of studies the responses of rats and mice to inhaled carbonyl iron or silica particles were evaluated. Three strains of mice and two strains of rats were exposed acutely to CI particles at identical aerosol concentrations. Two of the mouse strains developed transient lung inflammatory responses while CDR and Long-Evans rats did not. Moreover, AM chemotaxis and phagocytosis in rats were significantly increased compared to the mouse strains (P < 0.05). In another experiment, a single exposure to silica particles produced sustained inflammation in the lungs of rats, characterized by neutrophil emigration, and increased levels of extracellular enzymes and protein. In contrast, silica produced only a transient inflammatory response in the lungs of both strains of mice and this finding could not be accounted for by enhanced AM clearance of silica in mice. Our results demonstrate that acute pulmonary responses to the two inhaled particles were different in rats and mice. Whether either species simulates the human response remains to be determined.