![]() Therefore, we investigated the effect of a lower dose of DEP for a longer exposure period (90 days) in mice, focusing on the development and pathophysiological consequences of the inflammatory response. In this present study, we hypothesised that chronic exposure of mice to DEP would result in significant airway and lung parenchymal inflammation and changes in the alveolar structure. A pilot study using these samples showed a time dependent DEP-induced alveolar enlargement, reaching statistical significance at 60 days (data not shown). showed that instillation of 30 μg/10 μl of DEP over a period of 60 days induced respiratory tract inflammation and increased mucus content in the nose. In previous work from our laboratory, Yoshizaki et al. that showed that particles emitted by traffic can worsen the development of emphysema in mice treated with papain, but hitherto it has not been demonstrated that air pollution alone could lead to structural alterations in the airspaces of the lungs. It is not known whether chronic exposure to air pollution leads to emphysematous changes in the lungs. Long term exposure to air pollution induces chronic inflammatory changes in the airways and increases the risk of airway obstruction. Nonsmoking-related risk factors such as genetic syndromes (α1-antitrypsin deficiency) as well as occupational exposures (outdoor pollution, second-hand smoke, biomass smoke), chronic asthma and tuberculosis also contribute to the development and progression of COPD. Indeed, it is estimated that 25-45% of the patients with COPD worldwide have never smoked. However, many COPD cases occur in non-smokers. Smoking has been considered the most important risk factor for chronic obstructive pulmonary disease (COPD). In urban centres, diesel exhaust particles (DEP) are considered to be the hazardous pollutants released from automotive engines due to their aerodynamic and chemical characteristics. Traffic is a major contributor to air pollution in cities, and traffic-related exposure has been shown to induce acute inflammation in humans, both in chamber studies using diesel exhaust and in “real-life” environments such as road tunnels. 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. 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. 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. 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. ResultsĭEP decreased IFN-γ levels in BAL (p = 0.03), but did not significantly alter IL-4, IL-10 and IL-13 levels. We measured the mean linear intercept (Lm), a measure of alveolar distension, and the mean airspace diameter (D0) and statistical distribution (D2). ![]() Bronchial thickness and the collagen/elastic fibers density were evaluated by morphometry. The presence of IL-13, MAC2+ macrophages, CD3+, CD4+, CD8+ T cells and CD20+ B cells in tissues was analysed by immunohistochemistry. The gene expression of Muc5ac in lung was evaluated by RT-PCR. Assessment of respiratory mechanics was performed. 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. Nasal instillations were performed five days a week, over a period of 90 days. 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). We evaluated the effects of chronic exposure to DEP at doses below those found in a typical bus corridor in Sao Paulo (150 μg/m 3). In healthy individuals, the timing and mechanisms of respiratory tract injuries caused by chronic exposure to air pollution remain to be clarified. 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.
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