Thrombin modulates synthesis of plasminogen activator inhibitor type 2 by
human peripheral blood monocytes
H Ritchie, A Jamieson and NA Booth
Department of Molecular and Cell Biology, University of Aberdeen, Scotland,
UK.
Fibrin deposition is characteristic of inflammatory diseases. The monocytes
is central to the inflammatory response and can affect fibrinolysis by
expression of urokinase (u-PA) and plasminogen activator inhibitor types 1
and 2 (PAI-1 and PAI-2, respectively). This study examines whether
thrombin, which promotes fibrin deposition, can contribute to fibrin
persistence by modulating expression of proteins of the fibrinolytic
system. Monocytes were isolated from human peripheral blood and analyzed
for PAI-2, PAI-1, and u-PA antigens by enzyme-linked immunosorbent assay
(ELISA). Monocytes responded to thrombin by increased expression of PAI-2
in a dose- and time-dependent manner, with maximal synthesis at a
concentration of 1 U/mL to 10 U/mL. This trend was also evident for PAI-1,
which was present at much lower levels. Thrombin and lipopolysaccharide
(LPS) stimulated comparable levels of PAI-2, studied at the antigen and
mRNA level. The dose effet of LPS on PAI-2 and PAI-1 was found to differ
from that of thrombin. The level of u-PA was undetectable by ELISA and
zymography in all samples. Thrombin stimulates PAI-2 synthesis by human
monocytes, therefore creating an imbalance in the fibrinolytic system. This
may contribute to persistence of fibrin, deposited during inflammation.
Volume 86,
Issue 9,
pp. 3428-3435,
11/01/1995
Copyright © 1995 by The American Society of Hematology
