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Protective effects of long pentraxin PTX3 on lung injury in a severe acute respiratory syndrome model in mice

Identifieur interne : 001F69 ( Main/Exploration ); précédent : 001F68; suivant : 001F70

Protective effects of long pentraxin PTX3 on lung injury in a severe acute respiratory syndrome model in mice

Auteurs : BING HAN [Canada] ; XUEZHONG MA [Canada] ; JIANHUA ZHANG [Canada] ; YU ZHANG [Canada] ; XIAOHUI BAI [Canada] ; David M. Hwang [Canada] ; Shaf Keshavjee [Canada] ; Gary A. Levy [Canada] ; Ian Mcgilvray [Canada] ; MINGYAO LIU [Canada]

Source :

RBID : Pascal:12-0400104

Descripteurs français

English descriptors

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 in vitro. Cytokine expression, severity of lung injury, leukocyte infiltration and inflammatory responses were examined in vivo. 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 in vitro. 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.


Affiliations:


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<affiliation wicri:level="4">
<inist:fA14 i1="04">
<s1>Department of Surgery, University of Toronto</s1>
<s2>Toronto, Ontario</s2>
<s3>CAN</s3>
<sZ>7 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<placeName>
<settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
<orgName type="university">Université de Toronto</orgName>
</affiliation>
<affiliation wicri:level="4">
<inist:fA14 i1="05">
<s1>Department of Medicine, University of Toronto</s1>
<s2>Toronto, Ontario</s2>
<s3>CAN</s3>
<sZ>8 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<placeName>
<settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
<orgName type="university">Université de Toronto</orgName>
</affiliation>
</author>
</analytic>
<series>
<title level="j" type="main">Laboratory investigation</title>
<title level="j" type="abbreviated">Lab. invest.</title>
<idno type="ISSN">0023-6837</idno>
<imprint>
<date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt>
<title level="j" type="main">Laboratory investigation</title>
<title level="j" type="abbreviated">Lab. invest.</title>
<idno type="ISSN">0023-6837</idno>
</seriesStmt>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Acute</term>
<term>Acute phase protein</term>
<term>Biotechnology</term>
<term>Clinical biology</term>
<term>Granulocyte</term>
<term>Infiltration</term>
<term>Inflammation</term>
<term>Lung</term>
<term>Lung disease</term>
<term>Models</term>
<term>Mouse</term>
<term>Neutrophil</term>
<term>Pentraxine PTX3</term>
<term>Protection</term>
<term>Protective factor</term>
<term>Severe acute respiratory syndrome</term>
<term>Transgenic animal</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Pathologie des poumons</term>
<term>Facteur de protection</term>
<term>Protection</term>
<term>Protéine phase aiguë</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Modèle</term>
<term>Animal transgénique</term>
<term>Souris</term>
<term>Aigu</term>
<term>Inflammation</term>
<term>Neutrophile</term>
<term>Granulocyte</term>
<term>Infiltration</term>
<term>Poumon</term>
<term>Biologie clinique</term>
<term>Biotechnologie</term>
<term>Pentraxine PTX3</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr">
<term>Animal transgénique</term>
<term>Biotechnologie</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">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 in vitro. Cytokine expression, severity of lung injury, leukocyte infiltration and inflammatory responses were examined in vivo. 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 in vitro. 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.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Canada</li>
</country>
<region>
<li>Ontario</li>
</region>
<settlement>
<li>Toronto</li>
</settlement>
<orgName>
<li>Université de Toronto</li>
</orgName>
</list>
<tree>
<country name="Canada">
<noRegion>
<name sortKey="Bing Han" sort="Bing Han" uniqKey="Bing Han" last="Bing Han">BING HAN</name>
</noRegion>
<name sortKey="Hwang, David M" sort="Hwang, David M" uniqKey="Hwang D" first="David M." last="Hwang">David M. Hwang</name>
<name sortKey="Hwang, David M" sort="Hwang, David M" uniqKey="Hwang D" first="David M." last="Hwang">David M. Hwang</name>
<name sortKey="Jianhua Zhang" sort="Jianhua Zhang" uniqKey="Jianhua Zhang" last="Jianhua Zhang">JIANHUA ZHANG</name>
<name sortKey="Keshavjee, Shaf" sort="Keshavjee, Shaf" uniqKey="Keshavjee S" first="Shaf" last="Keshavjee">Shaf Keshavjee</name>
<name sortKey="Keshavjee, Shaf" sort="Keshavjee, Shaf" uniqKey="Keshavjee S" first="Shaf" last="Keshavjee">Shaf Keshavjee</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="Levy, Gary A" sort="Levy, Gary A" uniqKey="Levy G" first="Gary A." last="Levy">Gary A. Levy</name>
<name sortKey="Mcgilvray, Ian" sort="Mcgilvray, Ian" uniqKey="Mcgilvray I" first="Ian" last="Mcgilvray">Ian Mcgilvray</name>
<name sortKey="Mcgilvray, Ian" sort="Mcgilvray, Ian" uniqKey="Mcgilvray I" first="Ian" last="Mcgilvray">Ian Mcgilvray</name>
<name sortKey="Mingyao Liu" sort="Mingyao Liu" uniqKey="Mingyao Liu" last="Mingyao Liu">MINGYAO LIU</name>
<name sortKey="Mingyao Liu" sort="Mingyao Liu" uniqKey="Mingyao Liu" last="Mingyao Liu">MINGYAO LIU</name>
<name sortKey="Mingyao Liu" sort="Mingyao Liu" uniqKey="Mingyao Liu" last="Mingyao Liu">MINGYAO LIU</name>
<name sortKey="Xiaohui Bai" sort="Xiaohui Bai" uniqKey="Xiaohui Bai" last="Xiaohui Bai">XIAOHUI BAI</name>
<name sortKey="Xuezhong Ma" sort="Xuezhong Ma" uniqKey="Xuezhong Ma" last="Xuezhong Ma">XUEZHONG MA</name>
<name sortKey="Yu Zhang" sort="Yu Zhang" uniqKey="Yu Zhang" last="Yu Zhang">YU ZHANG</name>
</country>
</tree>
</affiliations>
</record>

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