Protective effects of long pentraxin PTX3 on lung injury in a severe acute respiratory syndrome model in mice
Identifieur interne : 000943 ( PascalFrancis/Curation ); précédent : 000942; suivant : 000944Protective 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 :
- Laboratory investigation [ 0023-6837 ] ; 2012.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Animal transgénique, Biotechnologie.
English descriptors
- KwdEn :
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.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Protective effects of long pentraxin PTX3 on lung injury in a severe acute respiratory syndrome model in mice</title><author><name sortKey="Bing Han" sort="Bing Han" uniqKey="Bing Han" last="Bing Han">BING HAN</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Xuezhong Ma" sort="Xuezhong Ma" uniqKey="Xuezhong Ma" last="Xuezhong Ma">XUEZHONG MA</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>The Multi Organ Transplant Program, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Jianhua Zhang" sort="Jianhua Zhang" uniqKey="Jianhua Zhang" last="Jianhua Zhang">JIANHUA ZHANG</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>The Multi Organ Transplant Program, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Yu Zhang" sort="Yu Zhang" uniqKey="Yu Zhang" last="Yu Zhang">YU ZHANG</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Xiaohui Bai" sort="Xiaohui Bai" uniqKey="Xiaohui Bai" last="Xiaohui Bai">XIAOHUI BAI</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Hwang, David M" sort="Hwang, David M" uniqKey="Hwang D" first="David M." last="Hwang">David M. Hwang</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Laboratory Medicine and Pathobiology, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>6 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Keshavjee, Shaf" sort="Keshavjee, Shaf" uniqKey="Keshavjee S" first="Shaf" last="Keshavjee">Shaf Keshavjee</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>The Multi Organ Transplant Program, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><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></affiliation></author><author><name sortKey="Levy, Gary A" sort="Levy, Gary A" uniqKey="Levy G" first="Gary A." last="Levy">Gary A. Levy</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>The Multi Organ Transplant Program, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><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></affiliation></author><author><name sortKey="Mcgilvray, Ian" sort="Mcgilvray, Ian" uniqKey="Mcgilvray I" first="Ian" last="Mcgilvray">Ian Mcgilvray</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>The Multi Organ Transplant Program, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><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></affiliation></author><author><name sortKey="Mingyao Liu" sort="Mingyao Liu" uniqKey="Mingyao Liu" last="Mingyao Liu">MINGYAO LIU</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><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></affiliation><affiliation wicri:level="1"><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></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">12-0400104</idno><date when="2012">2012</date><idno type="stanalyst">PASCAL 12-0400104 INIST</idno><idno type="RBID">Pascal:12-0400104</idno><idno type="wicri:Area/PascalFrancis/Corpus">000045</idno><idno type="wicri:Area/PascalFrancis/Curation">000943</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Protective effects of long pentraxin PTX3 on lung injury in a severe acute respiratory syndrome model in mice</title><author><name sortKey="Bing Han" sort="Bing Han" uniqKey="Bing Han" last="Bing Han">BING HAN</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Xuezhong Ma" sort="Xuezhong Ma" uniqKey="Xuezhong Ma" last="Xuezhong Ma">XUEZHONG MA</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>The Multi Organ Transplant Program, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Jianhua Zhang" sort="Jianhua Zhang" uniqKey="Jianhua Zhang" last="Jianhua Zhang">JIANHUA ZHANG</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>The Multi Organ Transplant Program, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Yu Zhang" sort="Yu Zhang" uniqKey="Yu Zhang" last="Yu Zhang">YU ZHANG</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Xiaohui Bai" sort="Xiaohui Bai" uniqKey="Xiaohui Bai" last="Xiaohui Bai">XIAOHUI BAI</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Hwang, David M" sort="Hwang, David M" uniqKey="Hwang D" first="David M." last="Hwang">David M. Hwang</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Laboratory Medicine and Pathobiology, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>6 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Keshavjee, Shaf" sort="Keshavjee, Shaf" uniqKey="Keshavjee S" first="Shaf" last="Keshavjee">Shaf Keshavjee</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>The Multi Organ Transplant Program, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><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></affiliation></author><author><name sortKey="Levy, Gary A" sort="Levy, Gary A" uniqKey="Levy G" first="Gary A." last="Levy">Gary A. Levy</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>The Multi Organ Transplant Program, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><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></affiliation></author><author><name sortKey="Mcgilvray, Ian" sort="Mcgilvray, Ian" uniqKey="Mcgilvray I" first="Ian" last="Mcgilvray">Ian Mcgilvray</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>The Multi Organ Transplant Program, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><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></affiliation></author><author><name sortKey="Mingyao Liu" sort="Mingyao Liu" uniqKey="Mingyao Liu" last="Mingyao Liu">MINGYAO LIU</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><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></affiliation><affiliation wicri:level="1"><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></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><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0023-6837</s0></fA01><fA02 i1="01"><s0>LAINAW</s0></fA02><fA03 i2="1"><s0>Lab. invest.</s0></fA03><fA05><s2>92</s2></fA05><fA06><s2>9</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Protective effects of long pentraxin PTX3 on lung injury in a severe acute respiratory syndrome model in mice</s1></fA08><fA11 i1="01" i2="1"><s1>BING HAN</s1></fA11><fA11 i1="02" i2="1"><s1>XUEZHONG MA</s1></fA11><fA11 i1="03" i2="1"><s1>JIANHUA ZHANG</s1></fA11><fA11 i1="04" i2="1"><s1>YU ZHANG</s1></fA11><fA11 i1="05" i2="1"><s1>XIAOHUI BAI</s1></fA11><fA11 i1="06" i2="1"><s1>HWANG (David M.)</s1></fA11><fA11 i1="07" i2="1"><s1>KESHAVJEE (Shaf)</s1></fA11><fA11 i1="08" i2="1"><s1>LEVY (Gary A.)</s1></fA11><fA11 i1="09" i2="1"><s1>MCGILVRAY (Ian)</s1></fA11><fA11 i1="10" i2="1"><s1>MINGYAO LIU</s1></fA11><fA14 i1="01"><s1>Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></fA14><fA14 i1="02"><s1>The Multi Organ Transplant Program, University Health Network Toronto General Hospital</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></fA14><fA14 i1="03"><s1>Department of Laboratory Medicine and Pathobiology, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>6 aut.</sZ></fA14><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></fA14><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></fA14><fA20><s1>1285-1296</s1></fA20><fA21><s1>2012</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>8078</s2><s5>354000508199610040</s5></fA43><fA44><s0>0000</s0><s1>© 2012 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>40 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>12-0400104</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Laboratory investigation</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>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.</s0></fC01><fC02 i1="01" i2="X"><s0>002B24</s0></fC02><fC02 i1="02" i2="X"><s0>002A31</s0></fC02><fC02 i1="03" i2="X"><s0>002B05C02C</s0></fC02><fC02 i1="04" i2="X"><s0>215</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Pathologie des poumons</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Lung disease</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Pulmón patología</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Facteur de protection</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Protective factor</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Factor protector</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Protection</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Protection</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Protección</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Protéine phase aiguë</s0><s5>05</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Acute phase protein</s0><s5>05</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Proteína fase aguda</s0><s5>05</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Syndrome respiratoire aigu sévère</s0><s2>NM</s2><s5>06</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Severe acute respiratory syndrome</s0><s2>NM</s2><s5>06</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Síndrome respiratorio agudo severo</s0><s2>NM</s2><s5>06</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Modèle</s0><s5>08</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Models</s0><s5>08</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Modelo</s0><s5>08</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Animal transgénique</s0><s5>09</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Transgenic animal</s0><s5>09</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Animal transgénico</s0><s5>09</s5></fC03><fC03 i1="08" i2="X" l="FRE"><s0>Souris</s0><s5>11</s5></fC03><fC03 i1="08" i2="X" l="ENG"><s0>Mouse</s0><s5>11</s5></fC03><fC03 i1="08" i2="X" l="SPA"><s0>Ratón</s0><s5>11</s5></fC03><fC03 i1="09" i2="X" l="FRE"><s0>Aigu</s0><s5>12</s5></fC03><fC03 i1="09" i2="X" l="ENG"><s0>Acute</s0><s5>12</s5></fC03><fC03 i1="09" i2="X" l="SPA"><s0>Agudo</s0><s5>12</s5></fC03><fC03 i1="10" i2="X" l="FRE"><s0>Inflammation</s0><s5>17</s5></fC03><fC03 i1="10" i2="X" l="ENG"><s0>Inflammation</s0><s5>17</s5></fC03><fC03 i1="10" i2="X" l="SPA"><s0>Inflamación</s0><s5>17</s5></fC03><fC03 i1="11" i2="X" l="FRE"><s0>Neutrophile</s0><s5>18</s5></fC03><fC03 i1="11" i2="X" l="ENG"><s0>Neutrophil</s0><s5>18</s5></fC03><fC03 i1="11" i2="X" l="SPA"><s0>Neutrófilo</s0><s5>18</s5></fC03><fC03 i1="12" i2="X" l="FRE"><s0>Granulocyte</s0><s5>19</s5></fC03><fC03 i1="12" i2="X" l="ENG"><s0>Granulocyte</s0><s5>19</s5></fC03><fC03 i1="12" i2="X" l="SPA"><s0>Granulocito</s0><s5>19</s5></fC03><fC03 i1="13" i2="X" l="FRE"><s0>Infiltration</s0><s5>20</s5></fC03><fC03 i1="13" i2="X" l="ENG"><s0>Infiltration</s0><s5>20</s5></fC03><fC03 i1="13" i2="X" l="SPA"><s0>Infiltración</s0><s5>20</s5></fC03><fC03 i1="14" i2="X" l="FRE"><s0>Poumon</s0><s5>21</s5></fC03><fC03 i1="14" i2="X" l="ENG"><s0>Lung</s0><s5>21</s5></fC03><fC03 i1="14" i2="X" l="SPA"><s0>Pulmón</s0><s5>21</s5></fC03><fC03 i1="15" i2="X" l="FRE"><s0>Biologie clinique</s0><s5>23</s5></fC03><fC03 i1="15" i2="X" l="ENG"><s0>Clinical biology</s0><s5>23</s5></fC03><fC03 i1="15" i2="X" l="SPA"><s0>Biología clínica</s0><s5>23</s5></fC03><fC03 i1="16" i2="X" l="FRE"><s0>Biotechnologie</s0><s5>24</s5></fC03><fC03 i1="16" i2="X" l="ENG"><s0>Biotechnology</s0><s5>24</s5></fC03><fC03 i1="16" i2="X" l="SPA"><s0>Biotecnología</s0><s5>24</s5></fC03><fC03 i1="17" i2="X" l="FRE"><s0>Pentraxine PTX3</s0><s4>CD</s4><s5>96</s5></fC03><fC03 i1="17" i2="X" l="ENG"><s0>Pentraxine PTX3</s0><s4>CD</s4><s5>96</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Virose</s0></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Viral 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