title: Long pentraxin PTX3 deficiency worsens LPS-induced acute lung injury.
abstract: OBJECTIVE
  Long pentraxin PTX3 is an inflammatory mediator and a component of the humoral arm of innate immunity. PTX3 expression is increased in animals with acute lung injury (ALI) and in patients with sepsis or acute respiratory distress syndrome and is considered to be a potential biomarker for these diseases. However, the role of PTX3 in the pathogenesis of ALI is not fully understood. We hypothesized that PTX3, as an important immune modulator, may determine the severity of ALI.
  
  
  METHODS
  Lipopolysaccharide (LPS) was intra-tracheally administrated to PTX3 knock-out (PTX3-KO) and wild-type (WT) mice. Lung injury, neutrophil infiltration, cell death, fibrin deposition, and tissue factor expression in the lung were determined. Local and systemic inflammatory responses were assessed by measuring cytokines in the lung and plasma.
  
  
  RESULTS
  LPS instillation induced ALI in both PTX3-KO and WT mice. Interestingly, PTX3 deficiency significantly increased the magnitude/extent of lung injury compared to that in WT mice. The severe lung injury was accompanied by elevated neutrophil infiltration, cell death, and fibrin deposition in the lung. PTX3 deficiency also enhanced LPS-induced tissue factor expression/activation in the lung and increased tumor necrosis factor-alpha and monocyte chemoattractant protein-1 levels in the plasma.
  
  
  CONCLUSIONS
  Our data suggest that the endogenously expressed PTX3 plays a protective role in the pathogenesis of ALI and that a lack of PTX3 may enhance neutrophil recruitment, cell death, activation of coagulation cascades, and inflammatory responses in the lung.
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Jack J
authors.initials: JJ
authors.lastname: Haitsma
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Bai
authors.forename: Matthew
authors.initials: M
authors.lastname: Rubacha
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhang
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D000818:Animals; D030801:Animals, Genetically Modified; D001777:Blood Coagulation / Q000502:physiology; D002097:C-Reactive Protein / Q000378:metabolism*; D016923:Cell Death; D055786:Gene Knockout Techniques; D007249:Inflammation; D008070:Lipopolysaccharides; D051379:Mice; D020556:Neutrophil Infiltration; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D012720:Severity of Illness Index; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D008070:Lipopolysaccharides; D000683:Serum Amyloid P-Component; D000099153:Pentraxins