Review articleTwo-Way Interactions Between Inflammation and Coagulation
Section snippets
How Inflammation Causes Activation of Coagulation
Activation of coagulation and deposition of fibrin as a consequence of inflammation can be considered instrumental in containing inflammatory activity to the site of injury or infection, rendering this relationship physiologically efficient. However, inflammation-induced coagulation may also importantly contribute to disease, as illustrated by the coagulopathy that is associated with severe infection, such as sepsis, and also by the fact that thrombus formation on a ruptured atherosclerotic
How Coagulation Modulates Activation of Inflammation
Rather than being a one-way direction of inflammation leading to coagulation, both systems interact intensely, whereby coagulation can also importantly modulate inflammatory activity (Figure 1). Binding of coagulation proteases (such as thrombin or tissue factor) or anticoagulant proteins (such as activated protein C) to specific cell receptors on mononuclear cells or endothelial cells may affect cytokine production or inflammatory cell apoptosis. This cross-talk between the two systems is
Conclusions
Systemic inflammation will invariably lead to activation of the coagulation system, but vice versa, components of the coagulation system may markedly modulate the inflammatory response. Increasing evidence points to extensive cross-talk between the two systems at various points, with pivotal roles of tissue factor, thrombin, components of the protein C pathway, and fibrinolytic activators and inhibitors. Increased insight into the molecular mechanisms that play a role in the close relationship
References (49)
- et al.
TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin–thrombomodulin complex
J Biol Chem
(1996) - et al.
Tissue factor pathway inhibitor (TFPI) dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia
Blood
(2000) - et al.
The in vivo kinetics of tissue factor messenger RNA expression during human endotoxemia: relationship with activation of coagulation
Blood
(2000) - et al.
Aggravation of endotoxin-induced disseminated intravascular coagulation and cytokine activation in heterozygous protein C deficient mice
Blood
(2003) - et al.
Transfer of tissue factor from leukocytes to platelets is mediated by CD15 and tissue factor
Blood
(2000) - et al.
Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo
Blood
(2002) - et al.
C4b-binding protein exacerbates the host response to Escherichia coli
Blood
(1991) - et al.
The endothelial cell protein C receptor aids in host defense against Escherichia coli sepsis
Blood
(2000) - et al.
Experimental endotoxemia in humans: Analysis of cytokine release and coagulation, fibrinolytic, and complement pathways
Blood
(1990) - et al.
Metalloproteolytic release of endothelial cell protein C receptor
J Biol Chem
(2000)
The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel antiinflammatory mechanism
J Clin Invest
Efficacy and safety of recombinant human activated protein C for severe sepsis
N Engl J Med
Plasminogen activator and plasminogen activator inhibitor I release during experimental endotoxaemia in chimpanzees: effect of interventions in the cytokine and coagulation cascades
Clin Sci
uPAR: a versatile signalling orchestrator
Nat Rev Mol Cell Biol
Interleukin-1 blockade attenuates mediator release and dysregulation of the hemostatic mechanism during human sepsis
Arch Surg
Disturbed alveolar fibrin turnover during pneumonia is restricted to the site of infection
Eur Respir J
The lectin-like domain of thrombomodulin confers protection from neutrophil-mediated tissue damage by suppressing adhesion molecule expression via nuclear factor kappaB and mitogen-activated protein kinase pathways
J Exp Med
Thrombin signalling and protease-activated receptors
Nature
Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock
J Clin Invest
Activation of coagulation by administration of recombinant factor VIIa elicits interleukin-6 and interleukin-8 release in healthy human subjects
Clin Diagn Lab Immunol
Role of coagulation inhibitors in inflammation
Thromb Haemost
New mechanisms for vascular control of inflammation mediated by natural anticoagulant proteins
J Exp Med
Do-all receptor takes on coagulation, inflammation
Nat Med
Dysfunction of endothelial protein C activation in severe meningococcal sepsis
N Engl J Med
Cited by (277)
Hemostatic disorders in patients with infective endocarditis undergoing urgent surgical valve replacement – Rethinking current beliefs
2023, International Journal of CardiologyMissing links in preeclampsia cell model systems of endothelial dysfunction
2023, Trends in Molecular MedicineLong COVID: pathophysiological factors and abnormalities of coagulation
2023, Trends in Endocrinology and Metabolism