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Differential regulation of tissue factor and plasminogen activator inhibitor by human mononuclear cells

B S Schwartz1, J D Bradshaw

  • 1Department of Medicine, University of Wisconsin, Madison.

Blood
|October 1, 1989
PubMed

Insights

Immune cells can independently control fibrin-depositing proteins, tissue factor (TF) and plasminogen activator inhibitor-2 (PAI-2). This suggests greater flexibility in how monocytes regulate fibrin deposition during inflammation.

Area of Science:

  • Immunology
  • Hematology
  • Cell Biology

Background:

  • Fibrin deposition is characteristic of immune-mediated tissue lesions, indicating both coagulation activation and inhibited fibrinolysis.
  • Human monocytes produce tissue factor (TF) and plasminogen activator inhibitor-2 (PAI-2) in response to inflammatory stimuli like lipopolysaccharide (LPS), promoting fibrin deposition.
  • The cellular production of TF and PAI-2 is thought to be linked, contributing to fibrin persistence in inflammatory conditions.

Purpose of the Study:

  • To investigate the differential regulation of TF and PAI-2 in peripheral blood mononuclear cells (PBM) upon alloantigen stimulation.
  • To determine if the procoagulant (TF) and antifibrinolytic (PAI-2) effectors are coordinately or independently regulated in response to specific immune stimuli.

Main Methods:

  • Peripheral blood mononuclear cells (PBM) were stimulated with alloantigen.
  • TF activity and PAI-2 antigen/activity were measured.
  • Intracellular PAI-2 accumulation and degradation of exogenous PAI-2 were assessed.
  • Cellular proliferation (tritiated thymidine uptake) and mRNA profiles were analyzed to confirm stimulation and gene expression.

Main Results:

  • Alloantigen stimulation of PBM resulted in high TF activity without a corresponding increase in PAI-2 activity or antigen.
  • PBM did not accumulate intracellular PAI-2 or degrade added PAI-2, despite robust proliferation and TF production, confirming effective stimulation.
  • This divergent expression of TF and PAI-2 was sustained over 5 days and corroborated by mRNA analysis.

Conclusions:

  • Under alloantigen stimulation, mononuclear cells exhibit independent regulation of TF and PAI-2.
  • This suggests that the mechanisms controlling fibrin deposition in inflammatory mononuclear cells are more flexible than previously assumed.
  • Independent regulation allows for nuanced control of coagulation and fibrinolysis in immune-mediated tissue damage.

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