Pulmonary Macrophages Are Attracted to Inhaled Particles through Complement Activation

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Abstract
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.