HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Miyakawa, H. Articles by Suga, M. Search for Related Content PubMed PubMed Citation Articles by Miyakawa, H. Articles by Suga, M.

Effects of inducible nitric oxide synthase and xanthine oxidase inhibitors on SEB-induced interstitial pneumonia in mice

First Dept of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan

CORRESPONDENCE: M. Suga, First Dept of Internal Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto, 860-0811, Japan. Fax: 81 963710582. E-mail: suga@gpo.kumamoto-u.ac.jp

Keywords: autoimmune disease, inducible nitric oxide synthase, interstitial pneumonia, superantigen, xanthine oxidase

Received: July 31, 2001
Accepted November 29, 2001

This work was supported by a grant-in-aid for interstitial lung disease from the Ministry of Health, Labour and Welfare, Japan.

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 article has been cited by other articles:

				A. Boueiz, M. Damarla, and P. M. Hassoun Xanthine oxidoreductase in respiratory and cardiovascular disorders Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L830 - L840. [Abstract] [Full Text] [PDF]

				P. Pacher, A. Nivorozhkin, and C. Szabo Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol. Rev., March 1, 2006; 58(1): 87 - 114. [Abstract] [Full Text] [PDF]

				D. Ziora, K. Kaluska, and J. Kozielski An increase in exhaled nitric oxide is not associated with activity in pulmonary sarcoidosis Eur. Respir. J., October 1, 2004; 24(4): 609 - 614. [Abstract] [Full Text] [PDF]