thromboplastin and Cholangitis

Recently, we demonstrated that neutrophils express tissue factor (TF) in a model of acute obstructive cholangitis (AOC). However, the regulation of TF expression was not clear. In this study, we clarified the role of platelet-activating factor (PAF) in TF expression in neutrophils.. In a model of AOC, intravenous PAF antagonist, (SM-12502, 200 mg/kg) was administered 5 min before sepsis was induced. Normal saline was given as a control. Coagulation parameters and TF activity were monitored for 6 h. Thereafter, the liver was harvested for histological examination.. The percentage of neutrophils which stained positive for TF was significantly reduced by SM-12502 (74.9 +/- 19.3% vs 96.3 +/- 2.8%) (P < 0.01). The number of leukocytes infiltrating the liver was also significantly reduced. Coagulation abnormalities, TF activity, and focal necrosis of the hepatocytes were reduced by SM-12502.. SM-12502 inhibits TF expression in neutrophils which have infiltrated the liver sinusoids, reducing the subsequent infiltration of leukocytes. These results suggest that PAF plays an important role in the expression of TF in neutrophils in vivo.

Topics: Animals; Aspartate Aminotransferases; Blood Coagulation; Cholangitis; Disease Models, Animal; Leukocytes; Liver; Male; Neutrophils; Platelet Activating Factor; Rabbits; Thiazoles; Thiazolidines; Thromboplastin

Acute obstructive cholangitis (AOC) is one of the most fatal outcomes in sepsis, and frequently complicates disseminated intravascular coagulation (DIC). Recently we found that the plasma tissue factor (TF) level increased and changed in parallel with plasma markers of DIC in patients with AOC. To elucidate the role of TF in the pathogenesis of coagulopathy in AOC, we investigated the plasma levels of TF and its localization by immunohistochemical staining in rabbit models of AOC. Plasma TF activity significantly increased 3 h after the insult (0.63 +/- 0.1¿9 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 fluctuations 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 infiltrated into the liver sinusoids and around the bile duct, but not in the sinusoidal endothelial cells. A double immunofluorescence study revealed the concomitant presence of TF and fibrin at sites where macrophages 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 expression, leading to coagulopathy in the acute phase of obstructive cholangitis in rabbits.

Topics: Acute Disease; Animals; Blood Coagulation; Cell Movement; Cholangitis; Disease Models, Animal; Female; Immunohistochemistry; Liver; Macrophages; Neutrophils; Rabbits; Thromboplastin

Topics: Acute Disease; Adult; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Bilirubin; Blood Coagulation Tests; Cholangitis; Chronic Disease; Diagnosis, Differential; Female; Hepatitis A; Humans; Indicators and Reagents; Male; Methods; Middle Aged; Prothrombin Time; Thromboplastin