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CD40 engagement on endothelial cells promotes tissue factor-dependent procoagulant activity
L Zhou1, P Stordeur, A de Lavareille
1Laboratory of Haematology, Université Libre de Bruxelles, Brussels, Belgium.
Thrombosis and Haemostasis
|June 3, 1998
Summary
CD40 engagement on endothelial cells induces tissue factor-dependent procoagulant activity (PCA). This CD40/CD40L pathway may contribute to prothrombotic states in diseases involving activated endothelial and T cells.
Area of Science:
- Immunology
- Vascular Biology
- Hematology
Background:
- CD40 on endothelial cells mediates activation signals, upregulating adhesion molecules.
- The role of CD40 engagement in inducing procoagulant activity (PCA) on endothelial cells is not fully understood.
Purpose of the Study:
- To investigate the impact of CD40 engagement on the induction of tissue factor (TF)-dependent PCA on human umbilical vein endothelial cells (HUVECs).
Main Methods:
- Co-incubation of HUVECs with CD40L-transfected fibroblasts.
- Inhibition studies using anti-CD40 and anti-CD40L monoclonal antibodies (mAbs).
- Assay of PCA in factor VII-deficient plasma and measurement of TF mRNA accumulation.
- Incubation of activated HUVECs with T cells in the presence or absence of blocking mAbs.
Main Results:
- CD40 engagement by CD40L-transfected fibroblasts induced significant PCA in HUVECs.
- The induced PCA was TF-dependent, confirmed by plasma assays and TF mRNA levels.
- Blocking CD40/CD40L interactions with mAbs inhibited PCA induced by T cell interactions with activated HUVECs.
Conclusions:
- CD40 engagement on endothelial cells triggers TF-dependent PCA.
- The CD40/CD40L pathway plays a role in T cell-mediated induction of endothelial PCA.
- This pathway may be implicated in prothrombotic states during inflammatory diseases.