PM2.5-rich dust collected from the air in Fukuoka, Kyushu, Japan, can exacerbate murine lung eosinophilia

Abstract

PM2.5 can exacerbate asthma. Organic substances adsorbed on PM2.5-rich dust (PM2.5rd) were inactivated by heating at 360 °C. To characterize the role of organic substances, the effects of PM2.5rd and heated PM2.5-rich dust (H-PM2.5 rd) on allergic lung inflammation were investigated. BALB/c mice were intratracheally administered PM2.5rd or H-PM2.5rd with or without ovalbumin (OVA) four times at 2-week intervals. PM2.5rd, but not H-PM2.5rd, caused neutrophilic alveolitis and bronchitis. In the presence of OVA, PM2.5rd caused severe eosinophil infiltration and goblet cells proliferation in airways, along with a marked induction of the Th2 cytokines interleukin (IL)-4 and IL-13, and the eosinophil-related cytokine IL-5 in bronchoalveolar lavage fluid (BALF). OVA + H-PM2.5rd caused a weaker response. PM2.5rd showed adjuvant effects on OVA-specific immunoglobulin E (IgE) and IgG1 production, but H-PM2.5rd showed minimal effects. These findings suggested that PM2.5rd-bound substances might aggravate lung eosinophilia. To clarify the roles of TLR2, TLR4, and MyD88 on cytokine production in PM2.5rd, murine bone marrow-derived macrophages (BMDMs) from wild-type (WT), TLR2^−/−, TLR4^−/−, and MyD88^−/− BALB/c mice were stimulated with dust. Cytokine production was low or undetectable in TLR4^−/− cells, but occurred from TLR2^−/− cells, and production by MyD88^−/− cells was higher than by TLR4^−/− cells. These results suggest that TLR4 and TLR2 ligands (LPS and β-glucan, respectively) mainly contributed to cytokines production induced by PM2.5rd. In addition to chemical substances, PM2.5-bound microbial substances might act in inflammatory and allergic lung diseases.

• Asthma
• bone marrow macrophages
• lung eosinophilia
• knockout mice
• MyD88 deficient
• PM2.5-rich dust
• TLR deficient

Acknowledgements

The authors appreciate the vital contribution of students at Oita University of Nursing and Health Sciences in this research.

Declaration of interest

The authors report that they have no conflicts of interest. This study was supported in part by a grant (No. 22241011) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. This work was partly supported by the Global Environment Research Fund (5-1457) of the Ministry of the Environment, Japan.