title: Chronic exposure of diesel exhaust particles induces alveolar enlargement in mice.
abstract: BACKGROUND
  Diesel exhaust particles (DEPs) are deposited into the respiratory tract and are thought to be a risk factor for the development of diseases of the respiratory system. In healthy individuals, the timing and mechanisms of respiratory tract injuries caused by chronic exposure to air pollution remain to be clarified.
  
  
  METHODS
  We evaluated the effects of chronic exposure to DEP at doses below those found in a typical bus corridor in Sao Paulo (150 μg/m3). Male BALB/c mice were divided into mice receiving a nasal instillation: saline (saline; n = 30) and 30 μg/10 μL of DEP (DEP; n = 30). Nasal instillations were performed five days a week, over a period of 90 days. Bronchoalveolar lavage (BAL) was performed, and the concentrations of interleukin (IL)-4, IL-10, IL-13 and interferon-gamma (INF-γ) were determined by ELISA-immunoassay. Assessment of respiratory mechanics was performed. The gene expression of Muc5ac in lung was evaluated by RT-PCR. The presence of IL-13, MAC2+ macrophages, CD3+, CD4+, CD8+ T cells and CD20+ B cells in tissues was analysed by immunohistochemistry. Bronchial thickness and the collagen/elastic fibers density were evaluated by morphometry. We measured the mean linear intercept (Lm), a measure of alveolar distension, and the mean airspace diameter (D0) and statistical distribution (D2).
  
  
  RESULTS
  DEP decreased IFN-γ levels in BAL (p = 0.03), but did not significantly alter IL-4, IL-10 and IL-13 levels. MAC2+ macrophage, CD4+ T cell and CD20+ B cell numbers were not altered; however, numbers of CD3+ T cells (p ≤ 0.001) and CD8+ T cells (p ≤ 0.001) increased in the parenchyma. Although IL-13 (p = 0.008) expression decreased in the bronchiolar epithelium, Muc5ac gene expression was not altered in the lung of DEP-exposed animals. Although respiratory mechanics, elastic and collagen density were not modified, the mean linear intercept (Lm) was increased in the DEP-exposed animals (p ≤ 0.001), and the index D2 was statistically different (p = 0.038) from the control animals.
  
  
  CONCLUSIONS
  Our data suggest that nasal instillation of low doses of DEP over a period of 90 days results in alveolar enlargement in the pulmonary parenchyma of healthy mice.
authors.forename: Kelly
authors.initials: K
authors.lastname: Yoshizaki
authors.forename: Jôse Mára
authors.initials: JM
authors.lastname: Brito
authors.forename: Henrique T
authors.initials: HT
authors.lastname: Moriya
authors.forename: Alessandra C
authors.initials: AC
authors.lastname: Toledo
authors.forename: Sandra
authors.initials: S
authors.lastname: Ferzilan
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Ligeiro de Oliveira
authors.forename: Isabel D
authors.initials: ID
authors.lastname: Machado
authors.forename: Sandra H P
authors.initials: SH
authors.lastname: Farsky
authors.forename: Luiz F F
authors.initials: LF
authors.lastname: Silva
authors.forename: Milton A
authors.initials: MA
authors.lastname: Martins
authors.forename: Paulo H N
authors.initials: PH
authors.lastname: Saldiva
authors.forename: Thais
authors.initials: T
authors.lastname: Mauad
authors.forename: Mariangela
authors.initials: M
authors.lastname: Macchione
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001938:Brazil; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004547:Elastic Tissue / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D015656:Respiratory Mechanics / Q000187:drug effects; D013997:Time Factors; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D018836:Inflammation Mediators; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D012333:RNA, Messenger; D001335:Vehicle Emissions; D003094:Collagen
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