Heterogeneity of phagocytosis for inhaled versus instilled material

Animal experiments involving lung exposure to particles and toxins often use intratracheal instillation, although inhalation is more physiologically relevant to human respiratory tract exposures. Using nontoxic magnetic particles, we examined the particle content distribution within the macrophage population lavaged from the lungs of Syrian golden hamsters exposed either by inhalation or by intratracheal instillation. One to 3 days after iron oxide particle delivery to the lungs, lung macrophages were harvested from animals in pairs, one exposed by inhalation and one exposed by instillation. The macrophages were then magnetically fractionated according to magnetic iron oxide content by flowing the cell suspension through tubing placed within the magnetic field gradient of an electromagnet. Macrophages that had ingested the largest quantity of magnetic iron oxide preferentially collected adjacent to the tubing wall when the electromagnet was at its lowest current; those with fewer particulates collected at correspondingly higher amperages; those cells that were never pulled out of the flowing stream had little or no magnetic iron oxide content. Our results showed that 80% of the lavaged cell population from animals exposed by inhalation had measurable particle content, whereas by instillation, many cells (70%) received no dose at all. Exposure by inhalation produced a more even distribution of dose among lung macrophages. Macrophage intracellular motions showed a decrease when cell content exceeded 7 to 8% of cell volume. We conclude that the method of particle delivery to lungs can influence the dose distribution among lung macrophages.