Influence of Asian Dust Particles on Immune Adjuvant Effects and Airway Inflammation in Asthma Model Mice

Shimizu E (2014) Influence of Asian Dust Particles on Immune Adjuvant Effects and Airway Inflammation in Asthma Model Mice. PLoS ONE 9(11): e111831. doi:10.1371/journal.pone.0111831 Influence of Asian Dust Particles on Immune Adjuvant Effects and Airway Inflammation in Asthma Model Mice Jun Kurai 0 Masanari Watanabe 0 Katsuyuki Tomita 0 Hiroyuki Sano Akira Yamasaki 0 Eiji Shimizu 0 Qinghua Sun, The Ohio State University, United States of America 0 1 Department of Respiratory Medicine and Rheumatology, Tottori University Faculty of Medicine , Yonago, Tottori , Japan , 2 Department of Respiratory Medicine, Yonago Medical Center , Yonago, Tottori , Japan , 3 Department of Respiratory Medicine and Allergology, Kinki University Faculty of Medicine , Osaka-Sayama, Osaka , Japan Objective: An Asian dust storm (ADS) contains airborne particles that affect conditions such as asthma, but the mechanism of exacerbation is unclear. The objective of this study was to compare immune adjuvant effects and airway inflammation induced by airborne particles collected on ADS days and the original ADS soil (CJ-1 soil) in asthma model mice. Methods: Airborne particles were collected on ADS days in western Japan. NC/Nga mice were co-sensitized by intranasal instillation with ADS airborne particles and/or Dermatophagoides farinae (Df), and with CJ-1 soil and/or Df for 5 consecutive days. Df-sensitized mice were stimulated with Df challenge intranasally at 7 days after the last Df sensitization. At 24 hours after challenge, serum allergen specific antibody, differential leukocyte count and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were measured, and airway inflammation was examined histopathologically. Results: Co-sensitization with ADS airborne particles and Df increased the neutrophil and eosinophil counts in BALF. Augmentation of airway inflammation was also observed in peribronchiolar and perivascular lung areas. Df-specific serum IgE was significantly elevated by ADS airborne particles, but not by CJ-1 soil. Levels of interleukin (IL)-5, IL-13, IL-6, and macrophage inflammatory protein-2 were higher in BALF in mice treated with ADS airborne particles. Conclusion: These results suggest that substances attached to ADS airborne particles that are not in the original ADS soil may play important roles in immune adjuvant effects and airway inflammation. - Many studies have shown that exposure to particulate matter is associated with respiratory and cardiovascular morbidity or mortality [1] [2]. Asian dust storms (ADSs) originating from deserts in Mongolia, Northern China, and Kazakhstan often disperse dust over East Asia from spring until late autumn [3] [4] and ADS airborne particles increase the atmospheric particulate matter. The original ADS soil is transported over a long distance and becomes attached to chemical species such as sulfate (SO422) and nitrate (NO32), and to microbial agents [5,6]. Therefore, ADS airborne particles have a wide variety of substances on their surface. We have shown that ADS exposure can aggravate upper and lower tract respiratory symptoms and pulmonary dysfunction in adult patients with asthma [7] [8] [9]. Other studies have also found an association of an ADS with an increased risk of hospitalization in children with asthma [10] [11] [12]. These studies suggest that an ADS can exacerbate asthma, but the underlying mechanism remains unclear. ADS airborne particles increase airway inflammation and have immune adjuvant effects in ovalbumin (OVA)-induced asthma model mice [13] [14] [15]. However, these studies used Asian sand dust after heat treatment at 360uC for 30 min to inactivate certain substances (microbiological material) attached on particles. Our previous study showed that ADS airborne particles induced production of IL-8 in THP-G8 cells, but this effect did not occur with the original ADS soil. Thus, substances attached to ADS airborne particles may provoke exacerbation of asthma. However, the OVA-induced asthma mouse model uses aluminum as an adjuvant, but aluminum is an important constituent of Asian sand dust [13]. The innovative asthma mouse model developed by Shibamori et al. shows allergic asthma-like reactions after intranasal sensitization by Dermatophagoides farinae (Df) [16]. Thus, these mice may be more useful than the OVA-induced model because the Df-induced asthma model does not require an adjuvant such as aluminum. In this study, we explored the differences in immune adjuvant effects and airway inflammation between ADS airborne particles and original ADS soil, with the goal of investigating the mechanism of exacerbation of asthma caused by an ADS. The study was performed in Df-induced asthma model mice and Figure 1. Experimental protocol. NC/Nga mice were given intranasal (i.n.) applications of a mixture (ADS airborne particles and/or Df, or CJ-1 soil and/or Df) as sensitization for 5 consecutive days (days 04). At 7 days after the last allergen sensi (...truncated)