Metabolomics analysis reveals that benzo[a]pyrene, a component of PM2.5, promotes pulmonary injury by modifying lipid metabolism in a phospholipase A2-dependent manner in vivo and in vitro

作者：Zhang, Song-Yang; Shao, Danqing; Liu, Huiying; Feng, Juan; Feng, Baihuan; Song, Xiaoming; Zhao, Qian; Chu, Ming; Jiang, Changtao; Huang, Wei^*; Wang, Xian^*

来源：Redox Biology, 2017, 13: 459-469.

DOI：10.1016/j.redox.2017.07.001

• PM2.5
• Benzo[a]pyrene
• Pulmonary injury
• Phospholipase A2
• Alveolar type II cell

Particulate matter with an aerodynamic diameter less than 2.5 mu M (PM2.5) is one of the major environmental pollutants in China. In this study, we carried out a metabolomics profile study on PM2.5-induced inflammation. PM2.5 from Beijing, China, was collected and given to rats through intra-tracheal instillation in vivo. Acute pulmonary injury were observed by pulmonary function assessment and H.E. staining. The lipid metabolic profile was also altered with increased phospholipid and sphingolipid metabolites in broncho-alveolar lavage fluid (BALF) after PM2.5 instillation. Organic component analysis revealed that benzo[a]pyrene (BaP) is one of the most abundant and toxic components in the PM2.5 collected on the fiber filter. In vitro, BaP was used to treat A549 cells, an alveolar type II cell line. BaP (4 mu M, 24 h) induced inflammation in the cells. Metabolomics analysis revealed that BaP (4 mu M, 6 h) treatment altered the cellular lipid metabolic profile with increased phospholipid metabolites and reduced sphingolipid metabolites and free fatty acids (FFAs). The proportion of omega-3 polyunsaturated fatty acid (PUFA) was also decreased. Mechanically, BaP (4 mu M) increased the phospholipase A2 (PLA2) activity at 4 h as well as the mRNA level of Pla2g2a at 12 h. The pro-inflammatory effect of BaP was reversed by the cytosolic PLA2 (cPLA2) inhibitor and chelator of intracellular Ca2+. This study revealed that BaP, as a component of PM2.5, induces pulmonary injury by activating PLA2 and elevating lysophosphatidylcholine (LPC) in a Ca2+-dependent manner in the alveolar type II cells.

• 出版日期2017-10
• 单位北京大学