Monocyte Tissue Factor Expression: Lipopolysaccharide Induction and Roles in Pathological Activation of Coagulation

Abstract

The coagulation system is a part of the mammalian host defense system. Pathogens and pathogen components, such as bacterial lipopolysaccharide (LPS), induce tissue factor (TF) expression in circulating monocytes that then activates the coagulation protease cascade. Formation of a clot limits dissemination of pathogens, enhances the recruitment of immune cells and facilitates killing of pathogens. However, excessive activation of coagulation can lead to thrombosis. Here, we review studies on the mechanism of LPS induction of TF expression in monocytes and its contribution to thrombosis and disseminated intravascular coagulation. Binding of LPS to Toll-like receptor 4 on monocytes induces a transient TF expression that involves activation of intracellular signaling pathways and binding of various transcription factors, such as c-rel/p65 and c-Fos/c-Jun, to the TF promoter. Inhibition of TF in endotoxemia and sepsis models reduces activation of coagulation and improves survival. Studies with endotoxemic mice showed that hematopoietic cells and myeloid cells play major roles in the activation of coagulation. Monocyte TF expression is also increased after surgery. Activated monocytes release TF-positive extracellular vesicles (EVs) and levels of circulating TF-positive EVs are increased in endotoxemic mice and in patients with sepsis. More recently, it was shown that inflammasomes contribute to the induction of TF expression and activation of coagulation in endotoxemic mice. Taken together, these studies indicate that monocyte TF plays a major role in the LPS-induced activation of coagulation. Selective inhibition of monocyte TF expression may reduce pathologic activation of coagulation in sepsis and other diseases.

Tissue Factor and COVID-19 Associated Thrombosis

“…14 Notably, other studies have shown that activation of the NLRP3 inflammasome induces TF expression in monocytes and macrophages. 7 One study found that infection of human monocytes with SARS-CoV-2 led to increased TF expression (Figure 1B). 15 Platelets from patients with COVID-19 also induced TF expression in monocytes from healthy donors (Figure 1C).…”

“…In addition, TF expression is induced during injury and infection as part of the innate immune system. 7 For instance, virus infection increases TF expression in lung epithelial cells and induces expression in monocytes and vascular endothelial cells. 8 TF can also be released from cells on extracellular vesicles (EVs).…”

Thrombosis and Haemostasis 2023 Editors' Choice Papers

“…The impact of another inflammatory mechanism, namely, tissue factor expression in monocytes and its induction by lipopolysaccharide in a spectrum of disease, was the topic of the comprehensive review by Sachetto and Mackman. 77 Encompassing sepsis and venous thrombosis, this study offers valuable insights into these pathological conditions. Platelet procoagulant physiology and its related abnormalities naturally continue to represent a dynamic focus of research published in TH.…”

Lacticaseibacillus rhamnosus CRL1505 Peptidoglycan Modulates the Inflammation-Coagulation Response Triggered by Poly(I:C) in the Respiratory Tract

“…This response is known as the immuno-coagulative response [7] or thrombo-inflammation [8]. In this context, myeloid cells contribute to coagulation by the expression of tissue factor (TF) [9][10][11]. It was demonstrated that monocytes and macrophages express procoagulant TF to induce systemic coagulation activation and thrombosis during inflammatory processes [12] and sepsis [13].…”