Environ Health Perspect. 2010 May;118(5):640-6. doi: 10.1289/ehp.0901461. Epub 2010 Jan 08.
Particulate matter-induced airway hyperresponsiveness is lymphocyte dependent.
Environmental health perspectives
Vanessa Saunders, Patrick Breysse, Jennifer Clark, Alyssa Sproles, Melissa Davila, Marsha Wills-Karp
Affiliations
Affiliations
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229 , USA.
PMID: 20061214
PMCID: PMC2866679 DOI: 10.1289/ehp.0901461
Abstract
BACKGROUND: Exposure to airborne particulate matter (PM), a major component of air pollution, has been associated with increases in both exacerbations of and hospitalizations for asthma. We have previously shown that exposure to ambient PM collected in urban Baltimore (AUB) induces airway hyperresponsiveness (AHR), eosinophilic and neutrophilic inflammation, and the recruitment of T cells. However, the mechanism(s) by which it induces these features of asthma remains unknown.
OBJECTIVE: We investigated whether T lymphocytes play a role in AUB-induced AHR.
METHODS: We compared the effects of AUB exposure on the allergic phenotype in wild-type (WT) BALB/c mice and in mice deficient in recombinase-activating gene-1 (Rag1-/-) that lack mature lymphocytes.
RESULTS: We found that exposure of WT mice to AUB induced AHR concomitant with increases in the numbers of bronchoalveolar lavage (BAL) fluid lymphocytes, eosinophils, neutrophils, and mucus-containing cells in the lungs of WT mice. Interestingly, we show for the first time that these effects were associated with significant elevations in interleukin (IL)-17A, IL-17F, and T-helper 2 cell (TH2) (IL-13, IL-5) cytokine levels in lung cells, as well as reductions in the levels of the suppressive cytokine IL-10. Interestingly, Rag1-/- mice failed to develop AUB-induced AHR; however, AUB-induced BAL fluid cellularity, and mucus cell changes were only partially inhibited in Rag1-/- mice.
CONCLUSIONS: Taken together, our results suggest that AUB exposure increases the pathophysiological features of asthma via activation of lymphocyte-dependent pathways. These results provide a plausible biological mechanism for the strong association between PM exposure and the increased severity of asthma.
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