Antibody and immune complexes induce tissue factor production by human endothelial cells

Area of Science:

• Immunology
• Hematology
• Pathophysiology

Background:

• Patients with systemic lupus erythematosus (SLE) exhibit a higher incidence of arterial and venous thromboses.
• The underlying mechanisms driving thrombosis in SLE remain incompletely understood.
• Previous observations indicated that SLE sera contain antibodies and immune complexes capable of binding to endothelial cells.

Purpose of the Study:

• To investigate the effect of IgG complexes and sera from SLE patients on tissue factor production by endothelial cells.
• To determine if endothelial cell-derived tissue factor contributes to thrombotic events in SLE.

Main Methods:

• Human umbilical venous endothelial cells were incubated with heat-aggregated IgG (HA-IgG) and sera from SLE patients.
• Procoagulant activity was measured, and its dependence on time, cellular synthesis, and specific factors (Factor VII, anti-tissue factor antibody) was assessed.
• The role of platelets and different immunoglobulin fractions (monomeric IgG, IgA, IgM, IgG complexes) was examined.

Main Results:

• Incubation with HA-IgG led to a dose-dependent elaboration of procoagulant activity by endothelial cells, requiring 6-8 hours and de novo protein synthesis.
• Endothelial cells treated with sera from a majority of SLE patients (14/16) produced significantly increased amounts of tissue factor compared to normal sera.
• Fractions of SLE sera containing IgG complexes and monomeric immunoglobulins also stimulated greater tissue factor production.

Conclusions:

• Endothelial cells produce procoagulant tissue factor upon exposure to anti-endothelial cell antibodies or IgG-containing immune complexes found in SLE.
• This induced tissue factor production by endothelial cells at sites of immune vascular injury may be a key factor in the pathogenesis of thrombosis in SLE patients.