In vivo uptake of inhaled particles by airway phagocytes is enhanced in patients with mild asthma compared with normal volunteers
- 1Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
- 2Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
- 3Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
- Dr J C Lay, Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina, Chapel Hill, NC 27599-7310, USA; jcl{at}med.unc.edu
- Received 18 January 2008
- Accepted 24 October 2008
- Published Online First 3 December 2008
Abstract
Background: The uptake of inhaled particulate matter by airway phagocytes is an important defence mechanism contributing to the clearance of potentially toxic substances, including aeroallergens, from the lung. Since airway monocytes and macrophages can also function as antigen presenting cells, their ability to engulf materials deposited on the airway surface is of particular interest in patients with allergic asthma. To determine whether airway mononuclear phagocytes of patients with allergic asthma might have enhanced phagocytic activity, the in vivo uptake of inhaled radiolabelled particles was compared in 10 patients with mild allergic asthma and 8 healthy (non-allergic) individuals.
Methods: Phagocyte function was assessed by quantifying the proportion of radioactivity associated with cellular and supernatant fractions of induced sputum 2 h after inhalation of radiolabelled sulfur colloid particles. All subjects were pretreated with albuterol before sputum induction. A standardised breathing pattern was used to target aerosol deposition in the bronchial airways.
Results: In vivo particle uptake by airway cells was significantly greater in patients with asthma than in healthy volunteers (57.2% (95% CI 46.5% to 67.9%) vs 22.3% (95% CI 4.9% to 39.6%), p<0.01), as was in vitro phagocytosis of opsonised zymosan-A bioparticles. There was also a significant correlation (r = 0.85, p<0.01) between the percentage of sputum mononuclear phagocytes and the percentage uptake of particles in the patients with asthma but not in the control subjects.
Conclusions: In vivo particle uptake by airway macrophages is enhanced in persons with mild asthma. Enhanced uptake and processing of particulate antigens could contribute to the pathogenesis and progression of allergic airways disease and may contribute to the increased risk of disease exacerbation associated with particulate exposure.
Footnotes
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‣ Detailed descriptions of the methods used in this study are published online only at http://thorax.bmj.com/content/vol64/issue4
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Funding: This research was supported primarily through a grant from the National Institutes of Health (NHLBI-RO1 HL080337) and through a cooperative agreement with the United States Environmental Protection Agency. Although the research described in this article has been funded in part by the United States Environmental Protection Agency through cooperative agreement CR83346301 with the Center for Environmental Medicine, Asthma and Lung Biology at the University of North Carolina at Chapel Hill, it has not been subjected to the Agency’s required peer and policy review and therefore does not necessarily reflect the views of the Agency and no official endorsement should be inferred. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.
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Competing interests: None.
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Ethics approval: This study was approved by the University of North Carolina Committee for the Rights of Human Subjects (Institutional Review Board).
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Patient consent: Prior to participation in the study, all subjects read and signed an informed consent form after having the opportunity to ask questions regarding the purpose of the study, procedures and associated risks.
