MACROPHAGES AND NEUTROPHILS INFILTRATING INTO THE LIVER ARE RESPONSIBLE FOR TISSUE FACTOR EXPRESSION IN A RABBIT MODEL OF ACUTE OBSTRUCTIVECHOLANGITIS

Acute obstructive cholangitis (AOC) is one of the most fatal outcomes in sepsis, and frequently complicates disseminated intravascular coagu lation (DIC). Recently we found that the plasma tissue factor (TF) lev el increased and changed in parallel with plasma markers of DIC in pat ients with AOC. To elucidate the role of TF in the pathogenesis of coa gulopathy in AOC, we investigated the plasma levels of TF and its loca lization by immunohistochemical staining in rabbit models of AOC. Plas ma TF activity significantly increased 3 h after the insult (0.63 +/- 0.19 U/ml; p <0.01) compared with that beforehand (0.05 +/- 0.02 U/ml) , then reached a maximum level at 6 h (0.94 +/- 0.16 U/ml). The fluctu ations in plasma TF activity correlated with those of the coagulation parameters including platelet count, fibrinogen, prothrombin time, and antithrombin III activity. Immunohistochemically, enhanced expression of TF was mainly detected in macrophages and neutrophils that had inf iltrated into the liver sinusoids and around the bile duct, but not in the sinusoidal endothelial cells. A double immunofluorescence study r evealed the concomitant presence of TF and fibrin at sites where macro phages and neutrophils had conglomerated. However, we could not detect an apparent change in TF expression in the lung or kidney. These data suggest that macrophages and neutrophils infiltrating into the liver sinusoids and around the bile duct play a pivotal role in TF expressio n, leading to coagulopathy in the acute phase of obstructive cholangit is in rabbits.