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In Vivo Particle Uptake by Airway Macrophages in Healthy Volunteers

Center For Environmental Medicine, Asthma and Lung Biology, University of North Carolina, Chapel Hill, North Carolina; and Institute for Anatomy, University of Bern, Bern, Switzerland

Correspondence and requests for reprints should be addressed to Neil Alexis, Ph.D., Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina at Chapel Hill, 104 Mason Farm Rd., Chapel Hill, NC 27599-7310. E-mail: Neil_Alexis{at}med.unc.edu

We combined two techniques, radiolabeled aerosol inhalation delivery and induced sputum, to examine in vivo the time course of particle uptake by airway macrophages in 10 healthy volunteers. On three separate visits, induced sputum was obtained 40, 100, and 160 min after inhalation of radiolabeled sulfur colloid (SC) aerosol (Tc99 m-SC, 0.2 µm colloid size delivered in 6-µm droplets). On a fourth visit (control) with no SC inhalation, induced sputum was obtained and SC particles were incubated (37°C) in vitro with sputum cells for 40, 100, and 160 min (matching the times associated with in vivo sampling). Total and differential cell counts were recorded for each sputum sample. Compared with 40 min (6 ± 3%), uptake in vivo was significantly elevated at 100 (31 ± 5%) and 160 min (27 ± 4%); both were strongly associated with the number of airway macrophages (R = 0.8 and 0.7, respectively); and the number and proportion of macrophages at 40 min were significantly (P < 0.05) elevated compared with control (1,248 ± 256 versus 555 ± 114 cells/mg; 76 ± 6% versus 60 ± 5%). Uptake in vitro increased in a linear fashion over time and was maximal at 160 min (40 min, 12 ± 2%; 100 min, 16 ± 4%; 160 min, 24 ± 6%). These data suggest that airway surface macrophages in healthy subjects rapidly engulf insoluble particles. Further, macrophage recruitment and phagocytosis-modifying agents are factors in vivo that likely affect particle uptake and its time course.

Key Words: airway macrophages • induced sputum • mucociliary clearance • radiolabeled particles

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