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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Todoroki
H
H
Department of Surgery 1, University of Occupational and Environmental Health, Kitakyushu, Japan.
Higure
A
A
Okamoto
K
K
Okazaki
K
K
Nagafuchi
Y
Y
Takeda
S
S
Katoh
H
H
Itoh
H
H
Ohsato
K
K
Nakamura
S
S
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001777:Blood Coagulation; D002761:Cholangitis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D007962:Leukocytes / Q000473:pathology; D008099:Liver / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D013925:Thromboplastin / Q000378:metabolism*
D010972:Platelet Activating Factor; D013844:Thiazoles; D053778:Thiazolidines; C065776:3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one; D013925:Thromboplastin; D001219:Aspartate Aminotransferases