Mechanisms Underlying the "Particle Redistribution Phenomenon"

Abstract

ABSTRACT

Existing evidence has suggested that relatively insoluble particles are gradually redistributed among alveolar macrophages (AM) during alveolar clearance. To obtain information about mechanisms that may be operable in the redistribution of particles, lavaged lung free cell analyses and transmission electron microscopic (TEM) analyses of lung tissue were performed after rats were subchronically exposed to aerosolized titanium dioxide. Results from assessments of paniculate TiO₂-AM relationships during the clearance of the particles were consistent with a gradual redistribution of the TiO₂ among the lung's AM. TEM analyses indicated that the in situ autolysis of particle-containing AM is one mechanism involved in the redistribution of particles. Evidence was also obtained that indicated that the engulfment of one particle-containing phagocyte by another also occurs. Based on the observation of mitotic figures of particle-containing AM among lavaged lung free cells after particle deposition in the lung, as well as other lines of evidence that AM can replicate, another prominent mechanism of the particle redistribution phenomenon may be the in situ proliferation of particle-laden AM. In another component of the study, accordingly, we used the macrophage cell line J774A.1 as a surrogate for AM to investigate how different particulate loads in macrophages affect their abilities to proliferate in vitro, and to examine how particles are allocated from particle-laden parent macrophages to their progeny. The rate of proliferation of macrophages was unaffected by the containment of relatively high particulate burdens, and the allocation of particles to progeny macrophages appeared to be an uneven process. In the last component of our study, results from analyses for multinucleated AM among lavaged lung free cells during the alveolar clearance of three different burdens of polystyrene microspheres suggest that the fusion of particle-containing AM is not an important particle-"accreting" mechanism, which potentially could operate in opposition to the gradual dispersion of retained particles among the lung's AM population.