PTX3 as a potential biomarker of acute lung  injury: supporting evidence from animal  experimentation.
OBJECTIVE
Increased expression of long pentraxin 3 (PTX3) has been found in patients with sepsis or acute respiratory distress syndrome. Tissue factor (TF) activation plays an important role in the pathogenesis of acute lung injury. The present study sought to determine the relationship between PTX3 expression and TF activation in acute lung injury.


METHODS
Lung injury was induced by intratracheal instillation of lipopolysaccharide (LPS) in mice, and the PTX3 expression, TF activation and lung injury were determined. We also treated the lung injury with an anti-human tissue factor monoclonal antibody in human tissue factor knock-in (hTF-KI) mice.


RESULTS
Balb/c mice were challenged with increasing doses of LPS. After 24 h, PTX3 protein in the bronchioalveolar lavage fluid was increased in parallel with the severity of lung injury, and correlated with tissue factor (TF) activity. The expression and distribution of PTX3 and TF were further documented in detail 6 h after LPS (5 mg/kg) instillation. Treatment with anti-human TF monoclonal antibody dramatically attenuated LPS-induced lung injury, alveolar fibrin deposition and inflammatory cell infiltration in"humanized" hTF-KI mice 6 h after LPS challenge. The PTX3 expression was significantly decreased by the anti-coagulant therapy.


CONCLUSIONS
These results support the clinical finding that PTX3 may be a useful biomarker to the reflect severity of lung injury and provide effective therapies. The interplay between PTX3 and TF could be a potential mechanism that mediates lung injury.
He
Xiaolin
X
Latner Thoracic Surgery Research Laboratory, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
Han
Bing
B
Bai
Xiaohui
X
Zhang
Yu
Y
Cypel
Marcelo
M
Mura
Marco
M
Keshavjee
Shaf
S
Liu
Mingyao
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid; D002097:C-Reactive Protein / Q000235:genetics*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005819:Genetic Markers; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D018805:Sepsis / Q000453:epidemiology; D000099153:Pentraxins
D000911:Antibodies, Monoclonal; D002097:C-Reactive Protein; D005819:Genetic Markers; D009419:Nerve Tissue Proteins; D000099153:Pentraxins