title: Caspase 3 expression and plasma level of Fas ligand as apoptosis biomarkers in inflammatory endotoxemic lung injury.
abstract: OBJECTIVE
  The objective of this study is to evaluate if the immunohistochemical expression of a pulmonary apoptosis marker and plasma level of Fas ligand (FasL) correlates with the dose- and time-dependent severity of lung injury, induced by the administration of lipo-polysaccharide (LPS) in an endotoxemic rat model.
  
  
  METHODS
  Our study included 30 male Wistar rats, randomly divided into three groups: one control group (n=6) and two experimental groups (n=12÷group), in whom we induced endotoxemia by intraperitoneal injection of progressively increasing doses of LPS (5, 10 mg÷kg). We measured FasL plasma levels of the rats at different time points and analyzed the relationships with markers of lung injury. To investigate the level of caspase 3-protein expression, the immunohistochemistry of the lung tissue was assessed.
  
  
  RESULTS
  The median percentage of caspase 3-stained cells for the 5 mg÷kg LPS dose was 0.36%, for the 10 mg÷kg LPS dose was 0.4% and for the control group was 0.03% (p<0.0001). The elevated expression levels of caspase 3 were consistent with the altered lung morphologies observed (rs=0.88). LPS administration in rats resulted in a significant dose-dependent increase in the levels of plasma FasL (p<0.0001). These levels correlated with markers of lung injury: degree of hypoxemia (rs=-0.42), histological measured lung injury score (rs=0.72), the density of the caspase 3 staining cells in the immunohistochemistry assessment of apoptosis (rs=0.81) and with the plasma RAGE (receptor for advanced glycated end-products) values (rs=0.70).
  
  
  CONCLUSIONS
  Apoptosis is increased in edotoxemia induced lung injury and is likely to contribute to alveolar injury.
authors.affiliation: Department of Infectious Diseases, University of Medicine and Pharmacy of Tirgu Mures, Romania; ancameda.georgescu@umftgm.ro.
authors.forename: Raluca Ştefania
authors.initials: RŞ
authors.lastname: Fodor
authors.forename: Anca Meda
authors.initials: AM
authors.lastname: Georgescu
authors.forename: Bianca Liana
authors.initials: BL
authors.lastname: Grigorescu
authors.forename: Adrian Dan
authors.initials: AD
authors.lastname: Cioc
authors.forename: Mihaly
authors.initials: M
authors.lastname: Veres
authors.forename: Ovidiu Simion
authors.initials: OS
authors.lastname: Cotoi
authors.forename: Pal
authors.initials: P
authors.lastname: Fodor
authors.forename: Sanda Maria
authors.initials: SM
authors.lastname: Copotoiu
authors.forename: Leonard
authors.initials: L
authors.lastname: Azamfirei
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000378:metabolism*; D006801:Humans; D055370:Lung Injury / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D053222:Fas Ligand Protein; D053148:Caspase 3