title: Alterations in endothelial thrombomodulin expression in zymosan-induced lung injury.
abstract: BACKGROUND
  Acute respiratory distress syndrome (ARDS) is characterized by endothelial damage, neutrophil infiltration, and microvascular thrombosis. Products of the coagulation cascade, particularly thrombin, activate the endothelium with resulting polymorphonuclear neutrophil accumulation and thrombosis. This study assessed the changes in lung tissue endothelial thrombomodulin (TM) expression in a rat model of zymosan-induced remote lung injury.
  
  
  METHODS
  Rats were randomized into three groups: control, low-dose intraperitoneal zymosan, and high-dose intraperitoneal zymosan. The animals were killed 28 days later. Lungs were assessed for histopathology, immunohistochemically stained for TM, and analyzed for TM mRNA.
  
  
  RESULTS
  Animals developed a triphasic illness with ARDS in phase III. The lungs demonstrated normal TM immunoreactivity in areas of noninflamed lung but an almost complete absence of TM in areas of inflammation. Tissue TM mRNA decreased in association with the dose of zymosan.
  
  
  CONCLUSIONS
  Zymosan-induced lung injury is associated with decreased TM expression in areas of injury. This finding may be of pathophysiologic significance in human ARDS, and it needs to be further explored. We hypothesize that down-regulation of TM leads to a hypercoagulable endothelium, increased microvascular thrombosis, and subsequent lung injury.
authors.affiliation: Department of Surgery, University of Arkansas for Medical Sciences, Central Arkansas Veterans Healthcare System, Little Rock 72205, USA. conejohnb@uams.edu
authors.forename: John B
authors.initials: JB
authors.lastname: Cone
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Ferrer
authors.forename: Bonny H
authors.initials: BH
authors.lastname: Wallace
authors.forename: Junru
authors.initials: J
authors.lastname: Wang
authors.forename: Martin
authors.initials: M
authors.lastname: Hauer-Jensen
mesh_terms: D000818:Animals; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008168:Lung / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012131:Respiratory Insufficiency / Q000378:metabolism* / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D018180:Thrombomodulin / Q000378:metabolism*; D015054:Zymosan
chemical_list: D018180:Thrombomodulin; D015054:Zymosan