The mechanism of diesel exhaust particles-induced pulmonary inflammation.

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 08680582
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 環境影響評価(含放射線生物学)
• Research Institution: University of Shizuoka
• Principal Investigator: IKEDA Masahiko University of Shizuoka, Graduate School of Health Sciences, Research Associate, 生活健康科学研究科, 助手 (20232176)
• Project Period (FY): 1996 – 1997
• Keywords: Diesel exhaust particles / Nitric Oxide / Peroxynitrite / Broncho-alveolar lavage / Inflammation / Superoxide anion dadicals

Research Abstract

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.