Protective effects of long pentraxin PTX3 on lung injury in a severe acute respiratory syndrome model in mice
Identifieur interne : 000A41 ( Pmc/Checkpoint ); précédent : 000A40; suivant : 000A42Protective effects of long pentraxin PTX3 on lung injury in a severe acute respiratory syndrome model in mice
Auteurs : Bing Han ; Xuezhong Ma ; Jianhua Zhang ; Yu Zhang ; Xiaohui Bai ; David M. Hwang ; Shaf Keshavjee ; Gary A. Levy ; Ian Mcgilvray ; Mingyao LiuSource :
- Laboratory Investigation; a Journal of Technical Methods and Pathology [ 0023-6837 ] ; 2012.
Abstract
The outbreak of severe acute respiratory syndrome (SARS) in 2003 reinforces the potential of lethal pandemics of respiratory viral infections. The underlying mechanisms of SARS are still largely undefined. Long pentraxin PTX3, a humoral mediator of innate immunity, has been reported to have anti-viral effects. We examined the role of PTX3 in coronavirus murine hepatitis virus strain 1 (MHV-1)-induced acute lung injury, a previously reported animal model for SARS. PTX3-deficient mice (129/SvEv/C57BL6/J) and their wild-type (WT) littermates were intranasally infected MHV-1. These mice were also treated with recombinant PTX3. Effects of PTX3 on viral binding and infectivity were determined
Url:
DOI: 10.1038/labinvest.2012.92
PubMed: 22732935
PubMed Central: 3955193
Affiliations:
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<series><title level="j">Laboratory Investigation; a Journal of Technical Methods and Pathology</title>
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<front><div type="abstract" xml:lang="en"><p id="Par1">The outbreak of severe acute respiratory syndrome (SARS) in 2003 reinforces the potential of lethal pandemics of respiratory viral infections. The underlying mechanisms of SARS are still largely undefined. Long pentraxin PTX3, a humoral mediator of innate immunity, has been reported to have anti-viral effects. We examined the role of PTX3 in coronavirus murine hepatitis virus strain 1 (MHV-1)-induced acute lung injury, a previously reported animal model for SARS. PTX3-deficient mice (129/SvEv/C57BL6/J) and their wild-type (WT) littermates were intranasally infected MHV-1. These mice were also treated with recombinant PTX3. Effects of PTX3 on viral binding and infectivity were determined <italic>in vitro</italic>
. Cytokine expression, severity of lung injury, leukocyte infiltration and inflammatory responses were examined <italic>in vivo</italic>
. In PTX3 WT mice, MHV-1 induced PTX3 expression in the lung and serum in a time-dependent manner. MHV-1 infection led to acute lung injury with greater severity in PTX3-deficient mice than that in WT mice. PTX3 deficiency enhanced early infiltration of neutrophils and macrophages in the lung. PTX3 bound to MHV-1 and MHV-3 and reduced MHV-1 infectivity <italic>in vitro</italic>
. Administration of recombinant PTX3 significantly accelerated viral clearance in the lung, attenuated MHV-1-induced lung injury, and reduced early neutrophil influx and elevation of inflammatory mediators in the lung. Results from this study indicate a protective role of PTX3 in coronaviral infection-induced acute lung injury.</p>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Lab Invest</journal-id>
<journal-id journal-id-type="iso-abbrev">Lab. Invest</journal-id>
<journal-title-group><journal-title>Laboratory Investigation; a Journal of Technical Methods and Pathology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0023-6837</issn>
<issn pub-type="epub">1530-0307</issn>
<publisher><publisher-name>Nature Publishing Group US</publisher-name>
<publisher-loc>New York</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22732935</article-id>
<article-id pub-id-type="pmc">3955193</article-id>
<article-id pub-id-type="publisher-id">BFlabinvest201292</article-id>
<article-id pub-id-type="doi">10.1038/labinvest.2012.92</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Protective effects of long pentraxin PTX3 on lung injury in a severe acute respiratory syndrome model in mice</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Han</surname>
<given-names>Bing</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ma</surname>
<given-names>Xuezhong</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Jianhua</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Yu</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bai</surname>
<given-names>Xiaohui</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hwang</surname>
<given-names>David M</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Keshavjee</surname>
<given-names>Shaf</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff2">2</xref>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Levy</surname>
<given-names>Gary A</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
<xref ref-type="aff" rid="Aff5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>McGilvray</surname>
<given-names>Ian</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Liu</surname>
<given-names>Mingyao</given-names>
</name>
<address><email>mingyao.liu@utoronto.ca</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff4">4</xref>
<xref ref-type="aff" rid="Aff5">5</xref>
</contrib>
<aff id="Aff1"><label>1</label>
<institution-wrap><institution-id institution-id-type="GRID">grid.417184.f</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 0661 1177</institution-id>
<institution>Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Hospital,</institution>
</institution-wrap>
Toronto, Ontario Canada</aff>
<aff id="Aff2"><label>2</label>
<institution-wrap><institution-id institution-id-type="GRID">grid.417184.f</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 0661 1177</institution-id>
<institution>The Multi Organ Transplant Program, University Health Network Toronto General Hospital,</institution>
</institution-wrap>
Toronto, Ontario Canada</aff>
<aff id="Aff3"><label>3</label>
<institution-wrap><institution-id institution-id-type="GRID">grid.17063.33</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 2157 2938</institution-id>
<institution>Department of Laboratory Medicine and Pathobiology,</institution>
<institution>University of Toronto,</institution>
</institution-wrap>
Toronto, Ontario Canada</aff>
<aff id="Aff4"><label>4</label>
<institution-wrap><institution-id institution-id-type="GRID">grid.17063.33</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 2157 2938</institution-id>
<institution>Department of Surgery,</institution>
<institution>University of Toronto,</institution>
</institution-wrap>
Toronto, Ontario Canada</aff>
<aff id="Aff5"><label>5</label>
<institution-wrap><institution-id institution-id-type="GRID">grid.17063.33</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 2157 2938</institution-id>
<institution>Department of Medicine,</institution>
<institution>University of Toronto,</institution>
</institution-wrap>
Toronto, Ontario Canada</aff>
</contrib-group>
<pub-date pub-type="epub"><day>25</day>
<month>6</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="ppub"><year>2012</year>
</pub-date>
<volume>92</volume>
<issue>9</issue>
<fpage>1285</fpage>
<lpage>1296</lpage>
<history><date date-type="received"><day>8</day>
<month>1</month>
<year>2012</year>
</date>
<date date-type="rev-recd"><day>25</day>
<month>4</month>
<year>2012</year>
</date>
<date date-type="accepted"><day>16</day>
<month>5</month>
<year>2012</year>
</date>
</history>
<permissions><copyright-statement>© United States and Canadian Academy of Pathology, Inc. 2012</copyright-statement>
<license><license-p>This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.</license-p>
</license>
</permissions>
<abstract id="Abs1"><p id="Par1">The outbreak of severe acute respiratory syndrome (SARS) in 2003 reinforces the potential of lethal pandemics of respiratory viral infections. The underlying mechanisms of SARS are still largely undefined. Long pentraxin PTX3, a humoral mediator of innate immunity, has been reported to have anti-viral effects. We examined the role of PTX3 in coronavirus murine hepatitis virus strain 1 (MHV-1)-induced acute lung injury, a previously reported animal model for SARS. PTX3-deficient mice (129/SvEv/C57BL6/J) and their wild-type (WT) littermates were intranasally infected MHV-1. These mice were also treated with recombinant PTX3. Effects of PTX3 on viral binding and infectivity were determined <italic>in vitro</italic>
. Cytokine expression, severity of lung injury, leukocyte infiltration and inflammatory responses were examined <italic>in vivo</italic>
. In PTX3 WT mice, MHV-1 induced PTX3 expression in the lung and serum in a time-dependent manner. MHV-1 infection led to acute lung injury with greater severity in PTX3-deficient mice than that in WT mice. PTX3 deficiency enhanced early infiltration of neutrophils and macrophages in the lung. PTX3 bound to MHV-1 and MHV-3 and reduced MHV-1 infectivity <italic>in vitro</italic>
. Administration of recombinant PTX3 significantly accelerated viral clearance in the lung, attenuated MHV-1-induced lung injury, and reduced early neutrophil influx and elevation of inflammatory mediators in the lung. Results from this study indicate a protective role of PTX3 in coronaviral infection-induced acute lung injury.</p>
</abstract>
<kwd-group xml:lang="en"><title>Keywords</title>
<kwd>acute lung injury</kwd>
<kwd>inflammatory response</kwd>
<kwd>neutrophil infiltration</kwd>
<kwd>pulmonary viral infection</kwd>
<kwd>transgenic mice</kwd>
</kwd-group>
<kwd-group kwd-group-type="npg-subject"><title>Subject terms</title>
<kwd>Recombinant protein therapy</kwd>
<kwd>Respiratory tract diseases</kwd>
<kwd>Viral infection</kwd>
</kwd-group>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© United States & Canadian Academy of Pathology 2012</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
<affiliations><list></list>
<tree><noCountry><name sortKey="Bai, Xiaohui" sort="Bai, Xiaohui" uniqKey="Bai X" first="Xiaohui" last="Bai">Xiaohui Bai</name>
<name sortKey="Han, Bing" sort="Han, Bing" uniqKey="Han B" first="Bing" last="Han">Bing Han</name>
<name sortKey="Hwang, David M" sort="Hwang, David M" uniqKey="Hwang D" first="David M" last="Hwang">David M. Hwang</name>
<name sortKey="Keshavjee, Shaf" sort="Keshavjee, Shaf" uniqKey="Keshavjee S" first="Shaf" last="Keshavjee">Shaf Keshavjee</name>
<name sortKey="Levy, Gary A" sort="Levy, Gary A" uniqKey="Levy G" first="Gary A" last="Levy">Gary A. Levy</name>
<name sortKey="Liu, Mingyao" sort="Liu, Mingyao" uniqKey="Liu M" first="Mingyao" last="Liu">Mingyao Liu</name>
<name sortKey="Ma, Xuezhong" sort="Ma, Xuezhong" uniqKey="Ma X" first="Xuezhong" last="Ma">Xuezhong Ma</name>
<name sortKey="Mcgilvray, Ian" sort="Mcgilvray, Ian" uniqKey="Mcgilvray I" first="Ian" last="Mcgilvray">Ian Mcgilvray</name>
<name sortKey="Zhang, Jianhua" sort="Zhang, Jianhua" uniqKey="Zhang J" first="Jianhua" last="Zhang">Jianhua Zhang</name>
<name sortKey="Zhang, Yu" sort="Zhang, Yu" uniqKey="Zhang Y" first="Yu" last="Zhang">Yu Zhang</name>
</noCountry>
</tree>
</affiliations>
</record>
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