Particulate Matter—Induced Airway Hyperresponsiveness Is Lymphocyte Dependent

• Published in: Environmental health perspectives 2010-05, Vol.118 (5), p.640-646
• Main Authors: Saunders, Vanessa, Breysse, Patrick, Clark, Jennifer, Sproles, Alyssa, Davila, Melissa, Wills-Karp, Marsha
• Format: Article
• Language: English
• Subjects: Air; Air Pollutants - toxicity; Allergies; Animals; Asthma; Asthma - etiology; Asthma - immunology; Asthma - physiopathology; Baltimore; Biological and medical sciences; Bronchial Hyperreactivity - etiology; Bronchial Hyperreactivity - immunology; Bronchial Hyperreactivity - physiopathology; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; Chronic obstructive pulmonary disease, asthma; Cytokines; Cytokines - biosynthesis; Diagnosis; Environment. Living conditions; Environmental pollutants toxicology; Female; Health aspects; Homeodomain Proteins - genetics; Homeodomain Proteins - physiology; Humans; Immunoglobulin E - blood; Inflammation; Lung - immunology; Lung - pathology; Lungs; Lymphocytes; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Knockout; Mucus; Neutrophils; Particles; Particulate Matter - toxicity; Pneumology; Public health. Hygiene; Public health. Hygiene-occupational medicine; Risk factors; T lymphocytes; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - physiology; Toxicology; Urban Health
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.0901461

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 elevation 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 patho-physiological 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.