The mechanism of diesel exhaust particles-induced pulmonary inflammation.

柴油机尾气颗粒诱发肺部炎症的机制。

• 批准号: 08680582
• 负责人: IKEDA Masahiko
• 金额: $ 1.47万
• 依托单位: University of Shizuoka
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08680582/
• 关键词: Diesel exhaust particles; Nitric Oxide; Peroxynitrite; Broncho-alveolar lavage; Inflammation; Superoxide anion dadicals; ディーゼル排気; 肺胞マクロファージ; 肺胞洗浄液

We have previously reported that diesel exhaust particles (DEP) impaired endothelium dependent relaxation (EDR). The mechanism of the impairment of EDR by DEP was investigated in this study, and we concluded that DEP scavenged NO from endothelium to block its physiological action on smooth muscle. Superoxide anion radical (O_2・-) from DEP appears to exert scavenging effect of NO,and peroxynitrite will be produced.When DEP were intratracheally administered to rat, macrophages, neutrophils, lymphocytes and eosinophils migrated in alveoli. Protein concentration in broncho-alveolar lavage fluid (BALF) was also increased. These results suggested that intratracheal administration of DEP induced pulmonary inflammation. Cells (macrophages and neutrophils) in BALF from DEP administered rat produced peroxynitrite. Peroxynitrite production was increased by 12-O-tetradecanoyl phorbol-13-acetate (TPA) stimulation, which stimulate O_2・- formation in those cells. This result indicated that O_2・- from DEP increased peroxynitrite formation in alveoli. However cells in BALF from control rat did not produce peroxynitrite before and after TPA stimulation.In conclusion, the mechanism of DEP-induced pulmonary inflammation is responsible for the formation of peroxynitrite formed by nitric oxide from cells in BALF and O_2・- from cells in BALF and DEP.The effect of DEP to scavenge NO from endothelium may also involve DEP-induced pulmonary inflammation by inhibiting the action of NO for anti-inflammatory effects.

我们以前曾报道过柴油机尾气颗粒（DEP）损害内皮依赖性舒张（EDR）。本研究探讨了DEP损伤EDR的机制，认为DEP通过清除内皮细胞NO，阻断其对平滑肌的生理作用。DEP产生的超氧阴离子自由基（O_2·-）具有清除NO的作用，并产生过氧亚硝基阴离子（O_2·-）。支气管肺泡灌洗液（BALF）中的蛋白质浓度也增加。这些结果表明，DEP的肺内给药诱导肺部炎症。给予DEP的大鼠BALF中的细胞（巨噬细胞和中性粒细胞）产生过氧亚硝酸盐。12-O-十四烷酰佛波醇-13-乙酸酯（TPA）刺激细胞产生过氧亚硝酸盐，促进O_2·-生成。结果表明，DEP释放的O_2·-可促进肺泡内过氧亚硝基阴离子的形成。而对照组大鼠BALF细胞在TPA刺激前后均不产生过氧亚硝基阴离子。DEP诱导肺部炎症的机制是通过支气管肺泡灌洗液（BALF）中细胞一氧化氮（NO）和支气管肺泡灌洗液（BALF）和DEP中细胞O_2·-形成过氧化亚硝酸盐来实现的。DEP清除内皮细胞中NO的作用也可能与DEP诱导肺部炎症有关，其机制是通过抑制NO的抗氧化作用来实现的。炎症效应。