Increased serum levels and sinusoidal expression of thrombomodulin in acute liver damage

Thrombomodulin (TM) is a surface glycoprotein of endothelial cells involved in both anticoagulation and antifibrinolysis, In this study, we assessed t he clinical significance of TM in acute liver damage by using a rat model i nduced by intraperitoneal injection of D-galactosamine (Gal-N). Serum TM le vels were measured with enzyme immunoassay utilizing rabbit anti-rat TM ant ibody. Simultaneously, immunohistochemical examination was performed using the same antibody. Serum TM levels increased significantly after the inject ion of Gal-N compared with preinjection levels, peaking from 48 to 72 hours after injection and normalizing by 168 hours. Changes in parenchymal damag e were synchronized with changes of TM, and changes of TM levels mirrored c hanges of liver weight. In immunohistochemical examination, TM immunoreacti vity was observed only on the endothelial surfaces of both the artery and p ortal vein within Glisson's sheath in controls. After injection of Gal-N, T M immunoreactivity was gradually intensified, especially around the necroti c area and the central veins. These findings disappeared with improvement o f parenchymal damage. Both the increase of serum TM levels and intensified TM immunoreactivity in the liver were synchronized with acute liver parench ymal damage induced by Gal-N. These findings on TM are related to endotheli al damage with parenchymal necrosis and liver regeneration interacting with both homeostasis of microcirculation and healing of parenchymal damage. (C ) 1999 Elsevier Science Ltd.