Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals.
Identifieur interne : 001C01 ( Main/Exploration ); précédent : 001C00; suivant : 001C02Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals.
Auteurs : T. Akaike [Japon] ; Y. Noguchi ; S. Ijiri ; K. Setoguchi ; M. Suga ; Y M Zheng ; B. Dietzschold ; H. MaedaSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 1996.
Descripteurs français
- KwdFr :
- Animaux, Antienzymes (pharmacologie), Arginine (analogues et dérivés), Arginine (pharmacologie), Espèces réactives de l'oxygène (métabolisme), Induction enzymatique, Interféron gamma (physiologie), Monoxyde d'azote (métabolisme), Mâle, Nitric oxide synthase (antagonistes et inhibiteurs), Nitric oxide synthase (biosynthèse), Pneumopathie virale (physiopathologie), Poumon (métabolisme), Radicaux libres, Souris, Spectroscopie de résonance de spin électronique, Superoxydes (métabolisme), Virus de la grippe A (pathogénicité), oméga-N-Méthylarginine.
- MESH :
- analogues et dérivés : Arginine.
- antagonistes et inhibiteurs : Nitric oxide synthase.
- biosynthèse : Nitric oxide synthase.
- métabolisme : Espèces réactives de l'oxygène, Monoxyde d'azote, Poumon, Superoxydes.
- pathogénicité : Virus de la grippe A.
- pharmacologie : Antienzymes, Arginine.
- physiologie : Interféron gamma.
- physiopathologie : Pneumopathie virale.
- Animaux, Induction enzymatique, Mâle, Radicaux libres, Souris, Spectroscopie de résonance de spin électronique, oméga-N-Méthylarginine.
English descriptors
- KwdEn :
- Animals, Arginine (analogs & derivatives), Arginine (pharmacology), Electron Spin Resonance Spectroscopy, Enzyme Induction, Enzyme Inhibitors (pharmacology), Free Radicals, Influenza A virus (pathogenicity), Interferon-gamma (physiology), Lung (metabolism), Male, Mice, Nitric Oxide (metabolism), Nitric Oxide Synthase (antagonists & inhibitors), Nitric Oxide Synthase (biosynthesis), Pneumonia, Viral (physiopathology), Reactive Oxygen Species (metabolism), Superoxides (metabolism), omega-N-Methylarginine.
- MESH :
- chemical , analogs & derivatives : Arginine.
- chemical , antagonists & inhibitors : Nitric Oxide Synthase.
- chemical , biosynthesis : Nitric Oxide Synthase.
- chemical , metabolism : Nitric Oxide, Reactive Oxygen Species, Superoxides.
- chemical , pharmacology : Arginine, Enzyme Inhibitors.
- metabolism : Lung.
- pathogenicity : Influenza A virus.
- chemical , physiology : Interferon-gamma.
- physiopathology : Pneumonia, Viral.
- Animals, Electron Spin Resonance Spectroscopy, Enzyme Induction, Free Radicals, Male, Mice, omega-N-Methylarginine.
Abstract
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.
DOI: 10.1073/pnas.93.6.2448
PubMed: 8637894
Affiliations:
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Le document en format XML
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Ijiri</name></author><author><name sortKey="Setoguchi, K" sort="Setoguchi, K" uniqKey="Setoguchi K" first="K" last="Setoguchi">K. Setoguchi</name></author><author><name sortKey="Suga, M" sort="Suga, M" uniqKey="Suga M" first="M" last="Suga">M. Suga</name></author><author><name sortKey="Zheng, Y M" sort="Zheng, Y M" uniqKey="Zheng Y" first="Y M" last="Zheng">Y M Zheng</name></author><author><name sortKey="Dietzschold, B" sort="Dietzschold, B" uniqKey="Dietzschold B" first="B" last="Dietzschold">B. Dietzschold</name></author><author><name sortKey="Maeda, H" sort="Maeda, H" uniqKey="Maeda H" first="H" last="Maeda">H. Maeda</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1996">1996</date><idno type="RBID">pubmed:8637894</idno><idno type="pmid">8637894</idno><idno type="doi">10.1073/pnas.93.6.2448</idno><idno type="wicri:Area/PubMed/Corpus">000400</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000400</idno><idno type="wicri:Area/PubMed/Curation">000400</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000400</idno><idno type="wicri:Area/PubMed/Checkpoint">000363</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000363</idno><idno type="wicri:Area/Ncbi/Merge">001326</idno><idno type="wicri:Area/Ncbi/Curation">001326</idno><idno type="wicri:Area/Ncbi/Checkpoint">001326</idno><idno type="wicri:doubleKey">0027-8424:1996:Akaike T:pathogenesis:of:influenza</idno><idno type="wicri:Area/Main/Merge">001C66</idno><idno type="wicri:Area/Main/Curation">001C01</idno><idno type="wicri:Area/Main/Exploration">001C01</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals.</title><author><name sortKey="Akaike, T" sort="Akaike, T" uniqKey="Akaike T" first="T" last="Akaike">T. Akaike</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Kumamoto University School of Medicine, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Microbiology, Kumamoto University School of Medicine</wicri:regionArea><wicri:noRegion>Kumamoto University School of Medicine</wicri:noRegion></affiliation></author><author><name sortKey="Noguchi, Y" sort="Noguchi, Y" uniqKey="Noguchi Y" first="Y" last="Noguchi">Y. Noguchi</name></author><author><name sortKey="Ijiri, S" sort="Ijiri, S" uniqKey="Ijiri S" first="S" last="Ijiri">S. Ijiri</name></author><author><name sortKey="Setoguchi, K" sort="Setoguchi, K" uniqKey="Setoguchi K" first="K" last="Setoguchi">K. Setoguchi</name></author><author><name sortKey="Suga, M" sort="Suga, M" uniqKey="Suga M" first="M" last="Suga">M. Suga</name></author><author><name sortKey="Zheng, Y M" sort="Zheng, Y M" uniqKey="Zheng Y" first="Y M" last="Zheng">Y M Zheng</name></author><author><name sortKey="Dietzschold, B" sort="Dietzschold, B" uniqKey="Dietzschold B" first="B" last="Dietzschold">B. Dietzschold</name></author><author><name sortKey="Maeda, H" sort="Maeda, H" uniqKey="Maeda H" first="H" last="Maeda">H. Maeda</name></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><imprint><date when="1996" type="published">1996</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Arginine (analogs & derivatives)</term><term>Arginine (pharmacology)</term><term>Electron Spin Resonance Spectroscopy</term><term>Enzyme Induction</term><term>Enzyme Inhibitors (pharmacology)</term><term>Free Radicals</term><term>Influenza A virus (pathogenicity)</term><term>Interferon-gamma (physiology)</term><term>Lung (metabolism)</term><term>Male</term><term>Mice</term><term>Nitric Oxide (metabolism)</term><term>Nitric Oxide Synthase (antagonists & inhibitors)</term><term>Nitric Oxide Synthase (biosynthesis)</term><term>Pneumonia, Viral (physiopathology)</term><term>Reactive Oxygen Species (metabolism)</term><term>Superoxides (metabolism)</term><term>omega-N-Methylarginine</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antienzymes (pharmacologie)</term><term>Arginine (analogues et dérivés)</term><term>Arginine (pharmacologie)</term><term>Espèces réactives de l'oxygène (métabolisme)</term><term>Induction enzymatique</term><term>Interféron gamma (physiologie)</term><term>Monoxyde d'azote (métabolisme)</term><term>Mâle</term><term>Nitric oxide synthase (antagonistes et inhibiteurs)</term><term>Nitric oxide synthase (biosynthèse)</term><term>Pneumopathie virale (physiopathologie)</term><term>Poumon (métabolisme)</term><term>Radicaux libres</term><term>Souris</term><term>Spectroscopie de résonance de spin électronique</term><term>Superoxydes (métabolisme)</term><term>Virus de la grippe A (pathogénicité)</term><term>oméga-N-Méthylarginine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Arginine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Nitric Oxide Synthase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Nitric Oxide Synthase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Nitric Oxide</term><term>Reactive Oxygen Species</term><term>Superoxides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Arginine</term><term>Enzyme Inhibitors</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Arginine</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Nitric oxide synthase</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Nitric oxide synthase</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Espèces réactives de l'oxygène</term><term>Monoxyde d'azote</term><term>Poumon</term><term>Superoxydes</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Influenza A virus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antienzymes</term><term>Arginine</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Interféron gamma</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Interferon-gamma</term></keywords><keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr"><term>Pneumopathie virale</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Electron Spin Resonance Spectroscopy</term><term>Enzyme Induction</term><term>Free Radicals</term><term>Male</term><term>Mice</term><term>omega-N-Methylarginine</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Induction enzymatique</term><term>Mâle</term><term>Radicaux libres</term><term>Souris</term><term>Spectroscopie de résonance de spin électronique</term><term>oméga-N-Méthylarginine</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Japon</li></country></list><tree><noCountry><name sortKey="Dietzschold, B" sort="Dietzschold, B" uniqKey="Dietzschold B" first="B" last="Dietzschold">B. Dietzschold</name><name sortKey="Ijiri, S" sort="Ijiri, S" uniqKey="Ijiri S" first="S" last="Ijiri">S. Ijiri</name><name sortKey="Maeda, H" sort="Maeda, H" uniqKey="Maeda H" first="H" last="Maeda">H. Maeda</name><name sortKey="Noguchi, Y" sort="Noguchi, Y" uniqKey="Noguchi Y" first="Y" last="Noguchi">Y. Noguchi</name><name sortKey="Setoguchi, K" sort="Setoguchi, K" uniqKey="Setoguchi K" first="K" last="Setoguchi">K. Setoguchi</name><name sortKey="Suga, M" sort="Suga, M" uniqKey="Suga M" first="M" last="Suga">M. Suga</name><name sortKey="Zheng, Y M" sort="Zheng, Y M" uniqKey="Zheng Y" first="Y M" last="Zheng">Y M Zheng</name></noCountry><country name="Japon"><noRegion><name sortKey="Akaike, T" sort="Akaike, T" uniqKey="Akaike T" first="T" last="Akaike">T. Akaike</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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