PMID- 8637894
OWN - NLM
STAT- MEDLINE
DCOM- 19960710
LR  - 20220330
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 93
IP  - 6
DP  - 1996 Mar 19
TI  - Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric 
      oxide and oxygen radicals.
PG  - 2448-53
AB  - The role of nitric oxide (NO) in the pathogenesis of influenza virus-induced 
      pneumonia in mice was investigated. Experimental influenza virus pneumonia was 
      produced with influenza virus A/Kumamoto/Y5/67(H2N2). Both the enzyme activity of 
      NO synthase (NOS) and mRNA expression of the inducible NOS were greatly increased 
      in the mouse lungs; increases were mediated by interferon gamma. Excessive 
      production of NO in the virus-infected lung was studied further by using electron 
      spin resonance (ESR) spectroscopy. In vivo spin trapping with 
      dithiocarbamate-iron complexes indicated that a significant amount of NO was 
      generated in the virus-infected lung. Furthermore, an NO-hemoglobin ESR signal 
      appeared in the virus-infected lung, and formation of NO-hemoglobin was 
      significantly increased by treatment with superoxide dismutase and was inhibited 
      by N(omega)-monomethyl-L-arginine (L-NMMA) administration. Immunohistochemistry 
      with a specific anti-nitrotyrosine antibody showed intense staining of alveolar 
      phagocytic cells such as macrophages and neutrophils and of intraalveolar exudate 
      in the virus-infected lung. These results strongly suggest formation of 
      peroxynitrite in the lung through the reaction of NO with O2-, which is generated 
      by alveolar phagocytic cells and xanthine oxidase. In addition, administration of 
      L-NMMA resulted in significant improvement in the survival rate of virus-infected 
      mice without appreciable suppression of their antiviral defenses. On the basis of 
      these data, we conclude that NO together with O2- which forms more reactive 
      peroxynitrite may be the most important pathogenic factors in influenza 
      virus-induced pneumonia in mice.
FAU - Akaike, T
AU  - Akaike T
AD  - Department of Microbiology, Kumamoto University School of Medicine, Japan.
FAU - Noguchi, Y
AU  - Noguchi Y
FAU - Ijiri, S
AU  - Ijiri S
FAU - Setoguchi, K
AU  - Setoguchi K
FAU - Suga, M
AU  - Suga M
FAU - Zheng, Y M
AU  - Zheng YM
FAU - Dietzschold, B
AU  - Dietzschold B
FAU - Maeda, H
AU  - Maeda H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Free Radicals)
RN  - 0 (Reactive Oxygen Species)
RN  - 11062-77-4 (Superoxides)
RN  - 27JT06E6GR (omega-N-Methylarginine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
SB  - IM
MH  - Animals
MH  - Arginine/analogs & derivatives/pharmacology
MH  - Electron Spin Resonance Spectroscopy
MH  - Enzyme Induction
MH  - Enzyme Inhibitors/pharmacology
MH  - Free Radicals
MH  - Influenza A virus/pathogenicity
MH  - Interferon-gamma/physiology
MH  - Lung/metabolism
MH  - Male
MH  - Mice
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Synthase/antagonists & inhibitors/biosynthesis
MH  - Pneumonia, Viral/*physiopathology
MH  - Reactive Oxygen Species/*metabolism
MH  - Superoxides/metabolism
MH  - omega-N-Methylarginine
PMC - PMC39817
EDAT- 1996/03/19 00:00
MHDA- 1996/03/19 00:01
PMCR- 1996/09/19
CRDT- 1996/03/19 00:00
PHST- 1996/03/19 00:00 [pubmed]
PHST- 1996/03/19 00:01 [medline]
PHST- 1996/03/19 00:00 [entrez]
PHST- 1996/09/19 00:00 [pmc-release]
AID - 10.1073/pnas.93.6.2448 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2448-53. doi: 10.1073/pnas.93.6.2448.