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<title xml:lang="en">Cathepsin G and Neutrophil Elastase Play Critical and Nonredundant Roles in Lung-Protective Immunity against
<named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
in Mice
<xref ref-type="fn" rid="FN1">
<sup></sup>
</xref>
</title>
<author>
<name sortKey="Hahn, Ines" sort="Hahn, Ines" uniqKey="Hahn I" first="Ines" last="Hahn">Ines Hahn</name>
<affiliation>
<nlm:aff id="aff1">Department of Experimental Pneumology</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Klaus, Anna" sort="Klaus, Anna" uniqKey="Klaus A" first="Anna" last="Klaus">Anna Klaus</name>
<affiliation>
<nlm:aff id="aff1">Department of Experimental Pneumology</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Janze, Ann Kathrin" sort="Janze, Ann Kathrin" uniqKey="Janze A" first="Ann-Kathrin" last="Janze">Ann-Kathrin Janze</name>
<affiliation>
<nlm:aff id="aff1">Department of Experimental Pneumology</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Steinwede, Kathrin" sort="Steinwede, Kathrin" uniqKey="Steinwede K" first="Kathrin" last="Steinwede">Kathrin Steinwede</name>
<affiliation>
<nlm:aff id="aff1">Department of Experimental Pneumology</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Ding, Nadine" sort="Ding, Nadine" uniqKey="Ding N" first="Nadine" last="Ding">Nadine Ding</name>
<affiliation>
<nlm:aff id="aff1">Department of Experimental Pneumology</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Bohling, Jennifer" sort="Bohling, Jennifer" uniqKey="Bohling J" first="Jennifer" last="Bohling">Jennifer Bohling</name>
<affiliation>
<nlm:aff id="aff1">Department of Experimental Pneumology</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Brumshagen, Christina" sort="Brumshagen, Christina" uniqKey="Brumshagen C" first="Christina" last="Brumshagen">Christina Brumshagen</name>
<affiliation>
<nlm:aff id="aff1">Department of Experimental Pneumology</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Serrano, Helene" sort="Serrano, Helene" uniqKey="Serrano H" first="Hélène" last="Serrano">Hélène Serrano</name>
<affiliation>
<nlm:aff id="aff2">INSERM U618, Proteases et Vectorisation Pulmonaires, Universite Francois Rabelais de Tours, Tours, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Gauthier, Francis" sort="Gauthier, Francis" uniqKey="Gauthier F" first="Francis" last="Gauthier">Francis Gauthier</name>
<affiliation>
<nlm:aff id="aff2">INSERM U618, Proteases et Vectorisation Pulmonaires, Universite Francois Rabelais de Tours, Tours, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Paton, James C" sort="Paton, James C" uniqKey="Paton J" first="James C." last="Paton">James C. Paton</name>
<affiliation>
<nlm:aff id="aff3">Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Welte, Tobias" sort="Welte, Tobias" uniqKey="Welte T" first="Tobias" last="Welte">Tobias Welte</name>
<affiliation>
<nlm:aff id="aff4">Clinic for Pneumology, Hannover School of Medicine, Hannover, Germany</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Maus, Ulrich A" sort="Maus, Ulrich A" uniqKey="Maus U" first="Ulrich A." last="Maus">Ulrich A. Maus</name>
<affiliation>
<nlm:aff id="aff1">Department of Experimental Pneumology</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt>
<idno type="wicri:source">PMC</idno>
<idno type="pmid">21911460</idno>
<idno type="pmc">3232647</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232647</idno>
<idno type="RBID">PMC:3232647</idno>
<idno type="doi">10.1128/IAI.05593-11</idno>
<date when="2011">2011</date>
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<title xml:lang="en" level="a" type="main">Cathepsin G and Neutrophil Elastase Play Critical and Nonredundant Roles in Lung-Protective Immunity against
<named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
in Mice
<xref ref-type="fn" rid="FN1">
<sup></sup>
</xref>
</title>
<author>
<name sortKey="Hahn, Ines" sort="Hahn, Ines" uniqKey="Hahn I" first="Ines" last="Hahn">Ines Hahn</name>
<affiliation>
<nlm:aff id="aff1">Department of Experimental Pneumology</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Klaus, Anna" sort="Klaus, Anna" uniqKey="Klaus A" first="Anna" last="Klaus">Anna Klaus</name>
<affiliation>
<nlm:aff id="aff1">Department of Experimental Pneumology</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Janze, Ann Kathrin" sort="Janze, Ann Kathrin" uniqKey="Janze A" first="Ann-Kathrin" last="Janze">Ann-Kathrin Janze</name>
<affiliation>
<nlm:aff id="aff1">Department of Experimental Pneumology</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Steinwede, Kathrin" sort="Steinwede, Kathrin" uniqKey="Steinwede K" first="Kathrin" last="Steinwede">Kathrin Steinwede</name>
<affiliation>
<nlm:aff id="aff1">Department of Experimental Pneumology</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Ding, Nadine" sort="Ding, Nadine" uniqKey="Ding N" first="Nadine" last="Ding">Nadine Ding</name>
<affiliation>
<nlm:aff id="aff1">Department of Experimental Pneumology</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Bohling, Jennifer" sort="Bohling, Jennifer" uniqKey="Bohling J" first="Jennifer" last="Bohling">Jennifer Bohling</name>
<affiliation>
<nlm:aff id="aff1">Department of Experimental Pneumology</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Brumshagen, Christina" sort="Brumshagen, Christina" uniqKey="Brumshagen C" first="Christina" last="Brumshagen">Christina Brumshagen</name>
<affiliation>
<nlm:aff id="aff1">Department of Experimental Pneumology</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Serrano, Helene" sort="Serrano, Helene" uniqKey="Serrano H" first="Hélène" last="Serrano">Hélène Serrano</name>
<affiliation>
<nlm:aff id="aff2">INSERM U618, Proteases et Vectorisation Pulmonaires, Universite Francois Rabelais de Tours, Tours, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Gauthier, Francis" sort="Gauthier, Francis" uniqKey="Gauthier F" first="Francis" last="Gauthier">Francis Gauthier</name>
<affiliation>
<nlm:aff id="aff2">INSERM U618, Proteases et Vectorisation Pulmonaires, Universite Francois Rabelais de Tours, Tours, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Paton, James C" sort="Paton, James C" uniqKey="Paton J" first="James C." last="Paton">James C. Paton</name>
<affiliation>
<nlm:aff id="aff3">Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Welte, Tobias" sort="Welte, Tobias" uniqKey="Welte T" first="Tobias" last="Welte">Tobias Welte</name>
<affiliation>
<nlm:aff id="aff4">Clinic for Pneumology, Hannover School of Medicine, Hannover, Germany</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Maus, Ulrich A" sort="Maus, Ulrich A" uniqKey="Maus U" first="Ulrich A." last="Maus">Ulrich A. Maus</name>
<affiliation>
<nlm:aff id="aff1">Department of Experimental Pneumology</nlm:aff>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Infection and Immunity</title>
<idno type="ISSN">0019-9567</idno>
<idno type="eISSN">1098-5522</idno>
<imprint>
<date when="2011">2011</date>
</imprint>
</series>
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<front>
<div type="abstract" xml:lang="en">
<p>Neutrophil serine proteases cathepsin G (CG), neutrophil elastase (NE), and proteinase 3 (PR3) have recently been shown to contribute to killing of
<named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
<italic>in vitro</italic>
. However, their relevance in lung-protective immunity against different serotypes of
<named-content content-type="genus-species">S. pneumoniae</named-content>
<italic>in vivo</italic>
has not been determined so far. Here, we examined the effect of CG and CG/NE deficiency on the lung host defense against
<named-content content-type="genus-species">S. pneumoniae</named-content>
in mice. Despite similar neutrophil recruitment, both CG knockout (KO) mice and CG/NE double-KO mice infected with focal pneumonia-inducing serotype 19
<named-content content-type="genus-species">S. pneumoniae</named-content>
demonstrated a severely impaired bacterial clearance, which was accompanied by lack of CG and NE but not PR3 proteolytic activity in recruited neutrophils, as determined using fluorescence resonance energy transfer (FRET) substrates. Moreover, both CG and CG/NE KO mice but not wild-type mice responded with increased lung permeability to infection with
<named-content content-type="genus-species">S. pneumoniae</named-content>
, resulting in severe respiratory distress and progressive mortality. Both neutrophil depletion and ablation of hematopoietic CG/NE in bone marrow chimeras abolished intra-alveolar CG and NE immunoreactivity and led to bacterial outgrowth in the lungs of mice, thereby identifying recruited neutrophils as the primary cellular source of intra-alveolar CG and NE. This is the first study showing a contribution of neutrophil-derived neutral serine proteases CG and NE to lung-protective immunity against focal pneumonia-inducing serotype 19
<named-content content-type="genus-species">S. pneumoniae</named-content>
in mice. These data may be important for the development of novel intervention strategies to improve lung-protective immune mechanisms in critically ill patients suffering from severe pneumococcal pneumonia.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Infect Immun</journal-id>
<journal-id journal-id-type="hwp">iai</journal-id>
<journal-id journal-id-type="pmc">iai</journal-id>
<journal-id journal-id-type="publisher-id">IAI</journal-id>
<journal-title-group>
<journal-title>Infection and Immunity</journal-title>
</journal-title-group>
<issn pub-type="ppub">0019-9567</issn>
<issn pub-type="epub">1098-5522</issn>
<publisher>
<publisher-name>American Society for Microbiology</publisher-name>
<publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">21911460</article-id>
<article-id pub-id-type="pmc">3232647</article-id>
<article-id pub-id-type="publisher-id">5593-11</article-id>
<article-id pub-id-type="doi">10.1128/IAI.05593-11</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Host Response and Inflammation</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Cathepsin G and Neutrophil Elastase Play Critical and Nonredundant Roles in Lung-Protective Immunity against
<named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
in Mice
<xref ref-type="fn" rid="FN1">
<sup></sup>
</xref>
</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Hahn</surname>
<given-names>Ines</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Klaus</surname>
<given-names>Anna</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Janze</surname>
<given-names>Ann-Kathrin</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Steinwede</surname>
<given-names>Kathrin</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ding</surname>
<given-names>Nadine</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bohling</surname>
<given-names>Jennifer</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Brumshagen</surname>
<given-names>Christina</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Serrano</surname>
<given-names>Hélène</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gauthier</surname>
<given-names>Francis</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Paton</surname>
<given-names>James C.</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Welte</surname>
<given-names>Tobias</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Maus</surname>
<given-names>Ulrich A.</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<aff id="aff1">
<label>1</label>
Department of Experimental Pneumology</aff>
<aff id="aff4">
<label>4</label>
Clinic for Pneumology, Hannover School of Medicine, Hannover, Germany</aff>
<aff id="aff2">
<label>2</label>
INSERM U618, Proteases et Vectorisation Pulmonaires, Universite Francois Rabelais de Tours, Tours, France</aff>
<aff id="aff3">
<label>3</label>
Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia</aff>
</contrib-group>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>Weiser</surname>
<given-names>J. N.</given-names>
</name>
<role>Editor</role>
</contrib>
</contrib-group>
<author-notes>
<corresp id="cor1">
<label>*</label>
Corresponding author. Mailing address:
<addr-line>Department of Experimental Pneumology, Hannover School of Medicine, Feodor-Lynen-Straße 21, Hannover 30625, Germany</addr-line>
. Phone:
<phone>49-511-532-9617</phone>
. Fax:
<fax>49-511-532-9616</fax>
. E-mail:
<email>Maus.Ulrich@mh-hannover.de</email>
.</corresp>
</author-notes>
<pub-date pub-type="ppub">
<month>12</month>
<year>2011</year>
</pub-date>
<volume>79</volume>
<issue>12</issue>
<fpage>4893</fpage>
<lpage>4901</lpage>
<history>
<date date-type="received">
<day>29</day>
<month>6</month>
<year>2011</year>
</date>
<date date-type="rev-request">
<day>27</day>
<month>7</month>
<year>2011</year>
</date>
<date date-type="accepted">
<day>2</day>
<month>9</month>
<year>2011</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2011, American Society for Microbiology. All Rights Reserved.</copyright-statement>
<copyright-year>2011</copyright-year>
<copyright-holder>American Society for Microbiology</copyright-holder>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zii01211004893.pdf"></self-uri>
<abstract>
<p>Neutrophil serine proteases cathepsin G (CG), neutrophil elastase (NE), and proteinase 3 (PR3) have recently been shown to contribute to killing of
<named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
<italic>in vitro</italic>
. However, their relevance in lung-protective immunity against different serotypes of
<named-content content-type="genus-species">S. pneumoniae</named-content>
<italic>in vivo</italic>
has not been determined so far. Here, we examined the effect of CG and CG/NE deficiency on the lung host defense against
<named-content content-type="genus-species">S. pneumoniae</named-content>
in mice. Despite similar neutrophil recruitment, both CG knockout (KO) mice and CG/NE double-KO mice infected with focal pneumonia-inducing serotype 19
<named-content content-type="genus-species">S. pneumoniae</named-content>
demonstrated a severely impaired bacterial clearance, which was accompanied by lack of CG and NE but not PR3 proteolytic activity in recruited neutrophils, as determined using fluorescence resonance energy transfer (FRET) substrates. Moreover, both CG and CG/NE KO mice but not wild-type mice responded with increased lung permeability to infection with
<named-content content-type="genus-species">S. pneumoniae</named-content>
, resulting in severe respiratory distress and progressive mortality. Both neutrophil depletion and ablation of hematopoietic CG/NE in bone marrow chimeras abolished intra-alveolar CG and NE immunoreactivity and led to bacterial outgrowth in the lungs of mice, thereby identifying recruited neutrophils as the primary cellular source of intra-alveolar CG and NE. This is the first study showing a contribution of neutrophil-derived neutral serine proteases CG and NE to lung-protective immunity against focal pneumonia-inducing serotype 19
<named-content content-type="genus-species">S. pneumoniae</named-content>
in mice. These data may be important for the development of novel intervention strategies to improve lung-protective immune mechanisms in critically ill patients suffering from severe pneumococcal pneumonia.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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