Fibronectin-adherent monocytes express tissue factor and tissue factor pathway inhibitor whereas endotoxin-stimulated...

Area of Science:

• Coagulation biology
• Monocyte and immune cell function
• Extravascular space physiology

Background:

• Monocytes initiate coagulation via tissue factor (TF) and express TF pathway inhibitor (TFPI).
• Lipopolysaccharide (LPS) stimulation increases monocyte TF but TFPI expression is debated.
• The role of fibronectin-adherent monocytes in TFPI expression and TF inhibition is unclear.

Purpose of the Study:

• To compare TF and TFPI expression in fibronectin-adherent versus LPS-stimulated non-adherent monocytes.

Main Methods:

• Monocytes were isolated and adhered to fibronectin or stimulated with LPS.
• TF and TFPI expression were quantified using RT-PCR, ELISA, and FX activation assays.

Main Results:

• Fibronectin-adherent monocytes showed marked upregulation of TF (mRNA, antigen, activity) and TFPI (mRNA, antigen).
• Fibronectin-adherent monocytes exhibited significant TFPI activity that inhibited TF procoagulant activity (PCA).
• LPS-stimulated monocytes expressed TF but minimal TFPI, with limited inhibition of TF activity.

Conclusions:

• Both monocyte types express TF, indicating a procoagulant phenotype.
• Fibronectin-adherent monocytes uniquely express sufficient TFPI to regulate thrombin generation and fibrin formation.
• TFPI expression by fibronectin-adherent monocytes is crucial for controlling coagulation in extravascular settings.