Effect of eicosanoids on induction of procoagulant activity by murine hepatitis virus strain 3 in vitro.
The development of hepatitis secondary to murine hepatitis virus strain 3 (MHV-3) infection correlates with the induction of macrophage procoagulant activity (PCA). 16,16 dimethyl prostaglandin E2 (dmPGE2) has previously been shown to inhibit the development of disease in this model and in parallel, inhibit induction of PCA, a macrophage effector molecule which has previously been shown to correlate with resistance/susceptibility to MHV-3 infection. These studies were undertaken to determine if inhibition of PCA was a specific property of dmPGE2 or if this property was shared by other eicosanoids including prostacyclin (PGI2), PGF2a and leukotriene B4 (LTB4). Furthermore, using the recently developed anti-PCA monoclonal antibody 3D4.3 (IgG2ak) which reacted with and inhibited functional PCA, studies were then undertaken to determine the mechanism by which PCA was inhibited by dmPGE2 (transcriptional, post-transcriptional or post-translational). Treatment with dmPGE2 resulted in inhibition of PCA induction compared with vehicle control over a range of 10(-12) to 10(-6) M. Utilizing the monoclonal antibody 3D4.3, it was demonstrated by Western immunoblot and immunofluorescence studies that although PCA was functionally inhibited by dmPGE2, it was still antigenically expressed as proteins of molecular weights 74 and 70 kd. Treatment of macrophages with PGI2, PGF2a or LTB4 failed to inhibit or augment PCA induction to MHV-3 stimulation at all concentrations tested (10(-12) to 10(-6) M). These results suggest that inhibition of PCA by dmPGE2 is a specific property of this eicosanoid and that its actions occur at a post-translational level.
Chung
S W
SW
Department of Medicine, University of Toronto, Canada.
Sinclair
S B
SB
Fung
L S
LS
Cole
E H
EH
Levy
G A
GA
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000818:Animals; D001779:Blood Coagulation Factors / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology; D015777:Eicosanoids / Q000494:pharmacology*; D011464:Epoprostenol / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006524:Hepatitis, Viral, Animal / Q000378:metabolism*; D015151:Immunoblotting; D007700:Kinetics; D007975:Leukotriene B4 / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D006517:Murine hepatitis virus; D010529:Peritoneal Cavity / Q000473:pathology
D001779:Blood Coagulation Factors; D015777:Eicosanoids; D007975:Leukotriene B4; D015237:Dinoprost; D011464:Epoprostenol; D015064:16,16-Dimethylprostaglandin E2