Migratory Behaviors of Alveolar Macrophages During the Alveolar Clearance of Light to Heavy Burdens of Particles

Abstract

We investigated the unstimulated and stimulated migratory activities of lavaged alveolar macrophages (AMs) in vitro over the course of alveolar clearance of three different mass lung burdens of microspheres. Our intent was to uncover potentially important relationships between the migratory behaviors of the AM and the retention kinetics of particles. Groups of adult, male Fischer-344 rats were intratracheally instilled with approximately 86 micrograms (low burden, LB), approximately 1 mg (medium burden, MB), or approximately 3.7 mg (high burden, HB) of polystyrene microspheres (2.13 microns diameter), or with carrier vehicle (phosphate buffered saline, PBS) alone. The lung retention kinetics of the particles were determined over an approximately 170 day period. On days 14, approximately 57, and approximately 85, lavaged AMs were assessed for their abilities to migrate through 5-microns pore membranes in response to inactivated rat serum (unstimulated condition) and yeast-activated rat serum (stimulated condition). The retention characteristics of the three burdens could be satisfactorily described by two-component, negative exponential equations. The kinetics of retention of the LB and MB were similar, although some evidence indicated the MB slightly retarded the lung clearance process. Deposition of the HB resulted in more marked prolongations of both the early, more rapid, and the slower, longer term components of alveolar clearance. The unstimulated migration indices of AMs from the particle-instilled lungs were generally not significantly different from those of AMs from PBS-instilled lungs except for a significant increase in the migration indices of LB AMs at the last assay time. The stimulated migration indices of MB and HB AMs were significantly decreased on assay days 14 and approximately 57. On day approximately 85, however, the migration indices of LB, MB, and HB AMs were all increased above the PBS AMs. Comparisons of the frequency distributions of particles in the unstimulated and stimulated AM that migrated to those in corresponding parent AM populations consistently indicated a preferential migration of particle-free AMs and of AMs with lesser loads of microspheres. The overall results of this study suggest that the unstimulated and stimulated migratory activities of particle-laden AMs are depressed in vitro. Our results also suggest that the migratory activities of generally particle-free AMs may be enhanced over a prolonged period of time following the deposition of particles in the lung.

Pulmonary and thoracic macrophage subpopulations and clearance of particles from the lung.

“…During the subsidence of the PMN response, particle-containing PMN are seen in the AM (Fig. 2), and when the PMN response has essentially totally subsided and only a small fraction of the lung burden has cleared from the lung, virtually all of the particles retained in the alveoli are contained in AM (63,64). Similarly, particle burdens in the AM can also be increased when they phagocytize other AM (see Fig.…”

“…As end points ofthis translocation pathway, the AM and particles are either swallowed or expectorated. Recognition of this "AM-associated particle clearance" or "AM-mediated particle clearance" process is mainly based on circumstantial evidence, such as observations of particle-containing macrophages on the luminal surfaces ofairways at times well after the particles were deposited in the lungs (89)(90)(91), and on inferential extensions ofexperimental results that have shown that the bulk ofparticles retained in the lung are associated with AM over the course of alveolar phase clearance (6,63,91). Further support for AM-associated particle clearance via the airways comes from findings that insoluble particles removed from the lung during alveolar phase clearance can be quantitiatively accounted for in the gastrointestinal tract and feces (92,93).…”

“…4). (63,64). The frequency distributions of microspheres in alveolar macrophage (AM) that migrated through 5-jim pore filters in response to yeast-activated serum at various times during the clearance ofthe low and high burdens ofparticles are summarized in Cand D, respectively (63).…”

“…order process resembling first-order mathematical depictions of the kinetics of alveolar phase clearance (6,63,64,101,105 (101,(108)(109)(110). While in vitro studies (63) have indeed indicated that the random and chemotactically stimulated migratory activities of AM are increasingly diminished as the load ofparticles they contain are increased, Lehnert and co-workers (63) found no consistent correlation between such particle burden-associated reductions in AM migration in vitro and the in vivo rates ofalveolar clearance oflow to higher lung burdens ofnoncytotoxic particles (Fig.…”

Cellular Defences of the Lung: Comparative Perspectives

“…PSMs remain motile up to a certain particle loading and beyond that the mobility is greatly inhibited (e.g. Yu et al, 1989;Lehnert et al, 1990;Kiama et al, 2008). For the avian PSMs (Kiama et al, 2008), the cells burst after ingesting high loads of polystylene particles .…”