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Previous studies have shown that inhaled particles and fibers that are small enough to pass through the conducting airways deposit preferentially at alveolar duct bifurcations in the distal lungs of exposed rats. Because it is well documented that anatomic and physiologic differences exist among common experimental animals that may influence deposition patterns, we compared inhaled particle deposition patterns in alveolar regions of four rodent species. Proximal alveolar regions of hamsters and guinea pigs contain rudimentary respiratory bronchioles, whereas in rats and mice, terminal bronchioles lead directly into alveolar ducts. Groups of animals from one strain each of rats, mice, hamsters, and guinea pigs were exposed to aerosols of carbonyl iron (CI) particles for 1 h at design concentrations of 100 mg/m3. Immediately after exposure, the lungs of sham- and CI-exposed animals were perfusion fixed through the vasculature. Subsequently, lung tissues from exposed animals was analyzed for iron concentration; data indicated that total lung deposition of iron particles was highest in mice and hamsters. In addition, scanning electron microscopy of dissected lung tissue revealed that particle deposition patterns in the proximal regions of the distal lung were similar for all species, although greater numbers of CI particles per bifurcation were deposited in rats and mice compared to hamsters (p less than 0.05) and greater numbers were deposited in hamsters compared to guinea pigs (p less than 0.05). The data suggest that the presence of undeveloped respiratory bronchioles in the lungs of hamsters and guinea pigs has little influence on distal lung particle deposition patterns. It remains to be determined whether inhaled particles are deposited at similar sites in the lungs of species with well-developed respiratory bronchioles such as cats, nonhuman primates, and humans.

Pulmonary macrophages play a central role in clearing inhaled particles from the lung. Previously, we showed that inhaled asbestos fibers activate complement-dependent chemotactic factors on alveolar surfaces to facilitate macrophage recruitment to sites of fiber deposition. In the studies presented here, we have tested a variety of inorganic particles for complement activation in vitro and correlated these data with results on particle-induced macrophage accumulation in vivo. We found that significant chemotactic activity was activated in rat serum and concentrated lavaged proteins by chrysotile and crocidolite asbestos, iron-coated chrysotile asbestos, fiberglass, and wollastonite fibers, as well as by carbonyl iron and zymosan particles. Ash from the Mt. St. Helens volcano did not induce chemotactic activity in either the serum or lavaged proteins. Rats were exposed to brief aerosols of each of the particles listed above (except zymosan). All the particle types studied were deposited primarily at first alveolar duct bifurcations. In addition, all of the particles, except Mt. St. Helens ash, induced at 48 h postexposure significant accumulations of macrophages at these sites. Time-course studies of carbonyl iron particle exposure demonstrated that iron induced a rapid macrophage response, but both particles and phagocytic macrophages were cleared from alveolar surfaces within 8 days after exposure. The Mt. St. Helens ash induced no macrophage accumulation at any time postexposure. We conclude that particles with a wide variety of physical characteristics are capable of activating complement and consequently attracting macrophages, both in vitro and in vivo. We suggest that complement activation is a mechanism through which pulmonary macrophages can detect inhaled particles on alveolar surfaces.

The morphology and phagocytic capacities of pulmonary macrophages recovered by lavage from normal rats were studied in vitro after incubation under various culture conditions. Most adherent macrophages (73 +/- 6%) were flat and exhibited ruffled surfaces. Phagocytosis of carbonyl iron beads by pulmonary macrophages was quantitated using secondary and backscattered electron microscopic techniques. Our results show that macrophage surface features correlate with the phagocytic capacity of the cells, that is, macrophages with ruffled membranes phagocytose a significantly greater number of iron beads than do smooth, unruffled cells (P less than or equal to 0.001). Moreover, an enhanced percentage of smooth cells (48%) was found in populations of tracheobronchial macrophages; this finding correlated with a reduced phagocytic potential. When the percentages of smooth cells were increased experimentally by incubating cells with silica or varying pH conditions, the number of macrophages devoid of carbonyl iron beads was enhanced. The results show that smooth macrophages are functionally impaired compared with ruffled cells. These studies form the basis for assessing functional alterations of macrophages exposed in vivo to inhaled toxic particulates such as chrysotile asbestos and silica.