Failure of a Simple Model of Alveolar Macrophage-Mediated Particle Clearance to Depict Particle–Alveolar Macrophage Relationships During Early Alveolar Phase Clearance

Abstract

Little experimental attention has been given to examining the relatlonship(s) between particles retained in the alveolar space compartment and the lung's population of alveolar macrophages (AM) during alveolar phase clearance. In this study, we quantitatively characterized the distributions of particles among lavageable AM over a 30 day period after the acute intratracheal instillation of ∼1.5 mg of 1.9 μm diam. polystyrene microspheres into the lungs of rats. Information obtained for particles retained in the lavageable AM compartment and partlcle-AM distribution data were collectively examined using a simple, first order kinetic model for AM removal from the lung. The results of our analyses suggest that a volume load of particles in a macrophage up to at least ∼360 μm3 does not inhibit the mobilization of macrophages from the alveolar compartment. Additionally, the kinetic analyses of the particle-macrophage distributions suggest that some macrophages that replenish those AM that are translocated from the lung on a continual basis during alveolar clearance are not and/or do not remain particle-free in the alveoli. This latter observation can be explained by a redistribution of particles among the lung's population of AM during alveolar phase clearance, although the influx of particle-bearing interstitial macrophages into the alveoli may also be a contributing factor.