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

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. 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. 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. Tissue factor expression in monocyte subsets varies significantly during health, endotoxemia and sepsis.

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Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AJS has been a co-applicant on funded grants on which Becton Dickinson Biosciences were also co-applicants. He is also Director of the National Institute for Health Research (NIHR) Newcastle Medtech and In Vitro Diagnostics Co-operative, which functions to support in vitro diagnostics companies, and in this capacity has worked with Becton Dickinson. HMHS are shareholders with Coagulation Profile, a university spin off diagnostic company. HMHS report grants from Bayer and Pfizer outside of the submitted work. HtC has received research support from Bayer and consultancy fees from Astra Zeneca, Galapagos, Viatris, Alveron, Pfizer and is shareholder from Coagulation Profile. All revenues are deposited at the CARIM institute for research development. KMM reports grants from Bayer during the conduct of this work. KMM reports personal fees from LEO Pharma and Pfizer outside of the submitted work, and conference attendance support from Sobi. WS declares conference attendance support from Chiesi Ltd. None of the other authors, including Cameron Lake, have any relevant disclosures