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Published in: Respiratory Research 1/2015

Open Access 01-12-2015 | Research

Chronic exposure of diesel exhaust particles induces alveolar enlargement in mice

Authors: Kelly Yoshizaki, Jôse Mára Brito, Henrique T Moriya, Alessandra C Toledo, Sandra Ferzilan, Ana Paula Ligeiro de Oliveira, Isabel D Machado, Sandra HP Farsky, Luiz FF Silva, Milton A Martins, Paulo HN Saldiva, Thais Mauad, Mariangela Macchione

Published in: Respiratory Research | Issue 1/2015

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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.

Conclusion

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.
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Metadata
Title
Chronic exposure of diesel exhaust particles induces alveolar enlargement in mice
Authors
Kelly Yoshizaki
Jôse Mára Brito
Henrique T Moriya
Alessandra C Toledo
Sandra Ferzilan
Ana Paula Ligeiro de Oliveira
Isabel D Machado
Sandra HP Farsky
Luiz FF Silva
Milton A Martins
Paulo HN Saldiva
Thais Mauad
Mariangela Macchione
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2015
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-015-0172-z

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