Published ahead of print on November 4, 2005, doi:10.1165/rcmb.2005-0373OC Am. J. Respir. Cell Mol. Biol., Volume 34, Number 3, March 2006, 305-313 A more recent version of this article appeared on March 1, 2006
Submitted on October 4, 2005 In Vivo Particle Uptake by Airway Macrophages in Healthy VolunteersNeil E Alexis1*,1 Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA, 2 Institute for Anatomy, University of Bern, Bern, Switzerland * To whom correspondence should be addressed. 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. following inhalation of radiolabeled sulfur colloid (SC) aerosol (Tc99m-SC, 0.2µm colloid size delivered in 6µm droplets). On a fourth visit (control) with no SC inhalation, induced sputum was obtained and SC particles were incubated (37 deg C) in vitro with sputum cells for 40, 100 and 160 minutes (matching the times associated with in vivo sampling). Total and differential cell counts were recorded for each sputum sample. Compared to 40 minutes (6 ± 3%), uptake in vivo was significantly elevated at 100 (31 ± 5%) and 160 minutes (27 ± 4%), both were strongly associated with the number of airway macrophages (R = 0.8), (R = 0.7), respectively, and the number and proportion of macrophages at 40 minutes were significantly (p<0.05) elevated compared to control (1248 ± 256 cells/mg vs. 555 ± 114 cells/mg; 76 ± 6% vs. 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.
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