Increased release of plasminogen activator inhibitor type 2 accompanies the
human mononuclear cell tissue factor response to lipopolysaccharide
BS Schwartz, MC Monroe and EG Levin
Department of Medicine (Hematology), University of Wisconsin, Madison
53706.
Human peripheral blood mononuclear cells (PBM) respond to
lipopolysaccharide (LPS) with increased release of a plasminogen activator
(PA) inhibitor. This response is dose dependent and parallels the
LPS-induced expression of PBM tissue factor activity. The PA inhibitors of
control and LPS-stimulated PBMs appear identical as both are identified by
antibodies to PA inhibitor type 2 of human placenta, but not by antibodies
to type 1 inhibitor of bovine aortic endothelial cells. The PA inhibitor is
specific for urokinase type PA as determined by the 125I-fibrin plate
assay, and direct cleavage of 125I- plasminogen; it does not effectively
inhibit tissue-type PA. The inhibitor forms an active site-dependent
complex with 125I-urokinase, which then demonstrates an increase in mol wt
from 33 kd to 68 kd on reduced sodium dodecyl sulfate (SDS) polyacrylamide
gels. PBMs neither secrete nor express active PA. Hence, the exposure of
PBMs to LPS results in conditions highly favorable to fibrin deposition and
persistence: increased procoagulant and antifibrinolytic activities,
accompanied by no measurable PA. Such modulation of these effectors may be
important in the pathogenesis of fibrin characteristically found in tissue
lesions of endotoxin-initiated processes.
Volume 71,
Issue 3,
pp. 734-741,
03/01/1988
Copyright © 1988 by The American Society of Hematology
