The immunomodulatory effects of diesel exhaust particles in asthma.

Ammonium persulfate (AP) causes occupational asthma (OA) and diesel exhaust particles (DEP) exacerbate asthma; however, the role of DEP in asthma due to chemical agents has not been assessed to date. Therefore, the present work aims to study the immunomodulatory effects of DEP in a mouse model of chemical asthma. BALB/c ByJ mice were randomly divided into four experimental groups. On days 1 and 8, mice were dermally sensitized with AP or saline. On days 15, 18 and 21, they received intranasal instillations of AP or saline. Two experimental groups received DEP on every of the three challenges. Airway hyperresponsiveness (AHR), lung mechanics, pulmonary inflammation in bronchoalveolar lavage, leukocyte numbers in total lung tissue, oxidative stress and optical projection tomography (OPT) studies were assessed. The AP-sensitized and challenged group showed asthma-like responses, such as airway hyperresponsiveness, increased levels of eosinophils and NKs and lower numbers of monocytes and CD11b-Ly6C- dendritic cells (DCs). Mice exposed to DEP alone showed increased levels of neutrophils and NKs, reduced numbers of monocytes and alveolar macrophages, and increased levels of CD11b + Ly6C- DCs. The AP sensitized and AP + DEP challenged group also showed asthma-like symptoms such as AHR, as well as increased numbers of eosinophils, neutrophils, CD11b + Ly6C- DCs and decreased levels of total and alveolar macrophages and tolerogenic DCs. Particle deposition was visualised using OPT. In the DEP group the particles were distributed relatively evenly, while in the AP + DEP group they were seen mainly in the large conducting airways. The results show that DEP exposure activates the innate immune response and, together with AP, exacerbates asthma immune hallmarks. This mouse model provides the first evidence of the capacity of DEPs to increase CD11b + Ly6C- (Th2-related) DCs. This study also demonstrates, for the first time, a differential deposition pattern of DEP in lungs depending on asthma status.