Possible role of platelet-activating factor in the in vivo expression of tissue factor in neutrophils

Background. Recently, we demonstrated that neutrophils express tissue facto r (TF) in a model of acute obstructive cholangitis (AOC). However, the regu lation of TF expression was not clear. In this study, we clarified the role of platelet-activating factor (PAF) in TF expression in neutrophils. Materials and methods. In a model of AOC, intravenous PAF antagonist, (SM-1 2502, 200 mg/kg) was administered 5 min before sepsis was induced. Normal s aline was given as a control. Coagulation parameters and TF activity were m onitored for 6 h. Thereafter, the liver was harvested for histological exam ination. Results. The percentage of neutrophils which stained positive for TF was si gnificantly 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 r educed. Coagulation abnormalities, TF activity, and focal necrosis of the h epatocytes were reduced by SM-12502. Conclusions. SM-12502 inhibits TF expression in neutrophils which have infi ltrated the liver sinusoids, reducing the subsequent infiltration of leukoc ytes. These results suggest that PAF plays an important role in the express ion of TF in neutrophils in vivo. (C) 1998 Academic Press.