title: Particulate matter-induced airway hyperresponsiveness is lymphocyte dependent.
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.
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229 , USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Saunders
authors.forename: Patrick
authors.initials: P
authors.lastname: Breysse
authors.forename: Jennifer
authors.initials: J
authors.lastname: Clark
authors.forename: Alyssa
authors.initials: A
authors.lastname: Sproles
authors.forename: Melissa
authors.initials: M
authors.lastname: Davila
authors.forename: Marsha
authors.initials: M
authors.lastname: Wills-Karp
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D015142:Baltimore; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D052638:Particulate Matter / Q000633:toxicity*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D014504:Urban Health
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D018398:Homeodomain Proteins; D052638:Particulate Matter; C064658:RAG-1 protein; D007073:Immunoglobulin E