DEPENDENCE ON O-2- GENERATION BY XANTHINE-OXIDASE OF PATHOGENESIS OF INFLUENZA-VIRUS INFECTION IN MICE

被引:287
作者
AKAIKE, T
ANDO, M
ODI, T
DOI, T
IJIRI, S
ARAKI, S
MAEDA, H
机构
[1] KUMAMOTO UNIV, SCH MED, DEPT MICROBIOL, KUMAMOTO 860, JAPAN
[2] KUMAMOTO UNIV, SCH MED, DEPT INTERNAL MED 1, KUMAMOTO 860, JAPAN
关键词
Free radicals; SOD; Viral pathogenesis; Xanthine oxidase;
D O I
10.1172/JCI114499
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
We evaluated various biochemical parameters in influenza virus-infected mice and focused on adenosine catabolism in the supernatant of bronchoalveolar lavage fluid (s-BALF), lung tissue, and serum (plasma). The activities of adenosine deaminase (ADA) and xanthine oxidase (XO), which generates O2-, were elevated in the s-BALF, lung tissue homogenate, and serum (plasma). The elevations were most remarkable in s-BALF and in lung tissue: We found a 170-fold increase in ADA activity and a 400-fold increase in XO activity as measured per volume of alveolar lavage fluid. The ratio of activity of XO to activity of xanthine dehydrogenase in s-BALF increased from 0.15±0.05 (control; no infection) to 1.06±0.13 on day 6 after viral infection. Increased levels of various adenosine catabolites (i.e., inosine, hypoxanthine, xanthine, and uric acid) in serum and s-BALF were confirmed. We also identified O2- generation from XO in s-BALF obtained on days 6 and 8 after infection, and the generation of O2- was enhanced remarkably in the presence of adenosine. Lastly, treatment with allopurinol (an inhibitor of XO) and with chemically modified superoxide dismutase (a scavenger of O2-) improved the survival rate of influenza virus-infected mice. These results indicate that generation of oxygen-free radicals by XO, coupled with catabolic supply of hypoxanthine from adenosine catabolism, is a pathogenic principle in influenza virus infection in mice and that a therapeutic approach by elimination of oxygen radicals thus seems possible.
引用
收藏
页码:739 / 745
页数:7
相关论文
共 39 条