Abstract
Introduction: Tissue factor expression on monocytes is implicated in the pathophysiology of sepsis-induced coagulopathy. How tissue factor is expressed by monocyte subsets (classical, intermediate and non-classical) is unknown. Methods: Monocytic tissue factor surface expression was investigated during three conditions. Primary human monocytes and microvascular endothelial cell co-cultures were used for in vitro studies. Volunteers received a bolus of lipopolysaccharide (2 ng/kg) to induce endotoxemia. Patients with sepsis, or controls with critical illness unrelated to sepsis, were recruited from four intensive care units. Results: Contact with endothelium and stimulation with lipopolysaccharide reduced the proportion of intermediate monocytes. Lipopolysaccharide increased tissue factor surface expression on classical and non-classical monocytes. Endotoxemia induced profound, transient monocytopenia, along with activation of coagulation pathways. In the remaining circulating monocytes, tissue factor was up-regulated in intermediate monocytes, though approximately 60 % of individuals (responders) up-regulated tissue factor across all monocyte subsets. In critically ill patients, tissue factor expression on intermediate and non-classical monocytes was significantly higher in patients with established sepsis than among non-septic patients. Upon recovery of sepsis, expression of tissue factor increased significantly in classical monocytes. Conclusion: Tissue factor expression in monocyte subsets varies significantly during health, endotoxemia and sepsis.
Original language | English |
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Pages (from-to) | 10-20 |
Number of pages | 11 |
Journal | Thrombosis Research |
Volume | 228 |
Issue number | 1 |
Early online date | 1 May 2023 |
DOIs | |
Publication status | Published - 1 Aug 2023 |
Keywords
- Endothelial cells
- Sepsis
- Monocytes
- Coagulation
- Tissue factor
- FACTOR PATHWAY INHIBITOR
- SEPTIC SHOCK
- COAGULATION
- ACTIVATION
- BLOOD
- COAGULOPATHY
- EFFICACY
- RELEASE
- MODELS
- SAFETY