PM2.5-induced lung inflammation in mice: Differences of inflammatory response in macrophages and type II alveolar cells.

Particulate matter 2.5 (<PM2.5 μm) leads to chronic obstructive pulmonary disease. In this study, biomarkers related to inflammation and oxidative stress in vitro and in vivo experiments were investigated to clarify the PM2.5-induced lung inflammation mechanisms. In an in vitro study using RAW264.7 cells, PM2.5 caused phosphorylation of nuclear factor-κB, p38 mitogen-activated protein kinase and extracellular response kinases, an increase of proinflammatory gene and protein expressions (e.g. monocyte chemotactic protein-1, tumor necrosis factor-α). These biomarkers were substantially attenuated by polymyxin B (PMB). PM2.5 induced heme oxygenase-1 (HO-1) gene, which was attenuated by N-acetylcysteine (NAC). However, the suppressive effects of NAC on inflammatory biomarkers were very weak. In bone marrow-derived macrophages (BMDMs) of wild-type BALB/c mice, the effects of PMB and NAC on PM2.5-induced inflammatory responses were similar to RAW264.7 cells. In BMDMs of MyD88-/- mice, PM2.5-induced proinflammatory mediators were substantially more attenuated. PM2.5 caused an increase of proinflammatory gene expressions (interleukin-6, cyclooxygenase 2) and HO-1 gene in MLE-12 cells (mouse alveolar cell line). These biomarkers were substantially attenuated by NAC, but not by PMB. When BALB/c mice were exposed intratracheally to 0.2 mg PM2.5, PM2.5 caused severe lung inflammation, an increase of neutrophils along with proinflammatory mediators in bronchoalveolar lavage fluid. The inflammation was attenuated by NAC, particularly by NAC + PMB, but not by PMB alone. These results indicate that macrophages may act sensitively to lipopolysaccharide (LPS) present in PM2.5 and release proinflammatory mediators via the LPS/MyD88 pathway. However, type II alveolar cells may react sensitively to oxidative stress induced by PM2.5 and cause inflammatory response. Therefore, overall, PM2.5 may cause predominantly oxidative stress-dependent inflammation rather than LPS/MyD88-dependent inflammation in type II alveolar cell-rich lungs.