PMID- 2155924
OWN - NLM
STAT- MEDLINE
DCOM- 19900417
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 85
IP  - 3
DP  - 1990 Mar
TI  - Dependence on O2- generation by xanthine oxidase of pathogenesis of influenza 
      virus infection in mice.
PG  - 739-45
AB  - 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.
FAU - Akaike, T
AU  - Akaike T
AD  - Department of Microbiology, Kumamoto University, Japan.
FAU - Ando, M
AU  - Ando M
FAU - Oda, T
AU  - Oda T
FAU - Doi, T
AU  - Doi T
FAU - Ijiri, S
AU  - Ijiri S
FAU - Araki, S
AU  - Araki S
FAU - Maeda, H
AU  - Maeda H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 11062-77-4 (Superoxides)
RN  - 63CZ7GJN5I (Allopurinol)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.17.3.2 (Xanthine Oxidase)
RN  - EC 3.5.4.4 (Adenosine Deaminase)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/metabolism
MH  - Adenosine Deaminase/analysis
MH  - Allopurinol/pharmacology
MH  - Animals
MH  - Bronchoalveolar Lavage Fluid/metabolism
MH  - Male
MH  - Mice
MH  - Orthomyxoviridae Infections/*etiology/metabolism
MH  - Superoxide Dismutase/pharmacology
MH  - Superoxides/*metabolism
MH  - Virus Replication
MH  - Xanthine Oxidase/analysis/*physiology
PMC - PMC296490
EDAT- 1990/03/01 00:00
MHDA- 1990/03/01 00:01
PMCR- 1990/03/01
CRDT- 1990/03/01 00:00
PHST- 1990/03/01 00:00 [pubmed]
PHST- 1990/03/01 00:01 [medline]
PHST- 1990/03/01 00:00 [entrez]
PHST- 1990/03/01 00:00 [pmc-release]
AID - 10.1172/JCI114499 [doi]
PST - ppublish
SO  - J Clin Invest. 1990 Mar;85(3):739-45. doi: 10.1172/JCI114499.