Tissue factor expression in monocyte subsets during human immunothrombosis, endotoxemia and sepsis

Area of Science:

• Immunology
• Hematology
• Pathophysiology

Background:

• Tissue factor (TF) on monocytes is crucial in sepsis-induced coagulopathy.
• Understanding TF expression across monocyte subsets is vital for sepsis research.

Purpose of the Study:

• To investigate TF surface expression on distinct monocyte subsets (classical, intermediate, non-classical) in various conditions.
• To elucidate the role of monocyte subsets in sepsis-related coagulopathy.

Main Methods:

• In vitro studies using human monocytes and endothelial cell co-cultures.
• In vivo endotoxemia model in volunteers induced by lipopolysaccharide (LPS).
• Analysis of monocyte TF expression in intensive care unit patients with sepsis or critical illness.

Main Results:

• LPS stimulation and endothelial contact altered monocyte subset proportions.
• TF expression increased on classical and non-classical monocytes post-LPS.
• Endotoxemia caused transient monocytopenia and coagulation activation.
• TF was upregulated on intermediate monocytes during endotoxemia; ~60% of individuals showed broad TF upregulation.
• Critically ill septic patients exhibited higher TF on intermediate and non-classical monocytes compared to non-septic controls.
• Classical monocyte TF expression increased upon sepsis recovery.

Conclusions:

• Monocyte subset TF expression is dynamic and varies significantly in health, endotoxemia, and sepsis.
• Distinct TF expression patterns on monocyte subsets contribute to sepsis pathophysiology.