Alterations in Endothelial Thrombomodulin Expression in Zymosan-Induced Lung Injury

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 groupscontrol, 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. CONCLUSION 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.