Dependence on O2- generation by xanthine oxidase of pathogenesis of influenza virus infection in mice

Takaaki Akaike, Masayuki Ando, Tatsuya Oda, Toshinori Doi, Sumiko Ijiri, Shukuro Araki, Hiroshi Maeda

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282 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)739-745
Number of pages7
JournalJournal of Clinical Investigation
Volume85
Issue number3
DOIs
Publication statusPublished - 1990 Mar
Externally publishedYes

Keywords

  • Free radicals
  • SOD
  • Viral pathogenesis
  • Xanthine oxidase

ASJC Scopus subject areas

  • Medicine(all)

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