RT Journal Article
SR Electronic
T1 Effects of inducible nitric oxide synthase and xanthine oxidase inhibitors on SEB-induced interstitial pneumonia in mice
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 447
OP 457
DO 10.1183/09031936.02.00265902
VO 19
IS 3
A1 H. Miyakawa
A1 K. Sato
A1 T. Shinbori
A1 T. Okamoto
A1 Y. Gushima
A1 M. Fujiki
A1 M. Suga
YR 2002
UL http://erj.ersjournals.com/content/19/3/447.abstract
AB The authors have previously reported that intratracheal instillation of staphylococcal enterotoxin‐B (SEB) induced interstitial pneumonia (IP) in autoimmune-prone mice. SEB-reactive T‐cells were critically involved in the development of IP in this model. Concern has arisen about the hazards of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the process of lung injury and fibrosis. Therefore, the involvement of nitric oxide (NO) and superoxide anion (O2−) in the pathogenesis of IP in this autoimmune-prone model has been investigated. Nitrite/nitrate levels were increased in bronchoalveolar lavage (BAL) fluid and serum from SEB-injected mice. The signal of the NO-(N‐(dithiocarboxy) sarcosine)2-Fe2+ complex was detected in the SEB-injected lung and whole blood by electron paramagnetic resonance (EPR) spectroscopy. NO production was significantly decreased by aminoguanidine (AG) treatment. Xanthine oxidase (XO) activity in the lung, BAL fluid, and plasma was increased with instillation of SEB, and 4‐amino‐6‐hydroxypyrazolo(3,4‐d)‐pyrimidine (AHPP) significantly inhibited XO activity. Moreover, both AG and AHPP significantly decreased production of pro-inflammatory cytokines, numbers of infiltrated cells in BAL fluid, and the area of thickened alveolar septa in the SEB-injected lung. In conclusion, the overproduction of nitric oxide and super oxide anion were implicated in the pathogenesis of interstitial pneumonia, and inducible nitric oxide synthase and xanthine oxidase inhibitors had protective effects against interstitial pneumonia in this model. This work was supported by a grant-in-aid for interstitial lung disease from the Ministry of Health, Labour and Welfare, Japan.