Differential regulation of tissue factor and plasminogen activator
inhibitor by human mononuclear cells
BS Schwartz and JD Bradshaw
Department of Medicine, University of Wisconsin, Madison.
Fibrin is a hallmark of immune-mediated tissue lesions. The presence of
fibrin in such lesions implies both the formation of fibrin via coagulation
and the accompanying restriction of fibrinolysis, allowing fibrin to
persist. Previous work has shown that human monocytes exposed to an
inflammatory stimulus such as lipopolysaccharide (LPS) produce both tissue
factor (TF) and plasminogen activator inhibitor--type 2 (PAI-2). These two
proteins favor fibrin deposition, and evidence implies that cellular
production of these two molecules may be linked. Another proinflammatory
process pertinent to immune-mediated tissue damage and fibrin deposition is
the response to alloantigen. Peripheral- blood mononuclear cells (PBM),
consisting of lymphocytes and monocytes together, responded to alloantigen
stimulation with differential expression of TF and PAI-2. PBM exposed to
alloantigen developed high levels of TF activity, with no concomitant
increase in PAI-2 activity or antigen. Alloantigen-stimulated PBM did not
accumulate intracellular PAI-2, nor did they degrade PAI-2 added to
cultures. This lack of PAI-2 production was not due to inadequate
stimulation, as tritiated thymidine uptake and TF production demonstrated
recognition of, and a vigorous reaction to, alloantigen. The divergent TF
and PAI-2 responses of PBM exposed to alloantigen was maintained over 5
days and was reflected by mRNA profiles. These results imply that under
specific physiologically relevant conditions, the procoagulant and
antifibrinolytic effectors of inflammatory mononuclear cells can be
independently regulated. This would imply more flexibility to monocyte
mechanisms that favor fibrin deposition than previously thought.
Volume 74,
Issue 5,
pp. 1644-1650,
10/01/1989
Copyright © 1989 by The American Society of Hematology
