Thrombomodulin/activated protein C system in septic disseminated intravascular coagulation

Table 1 Roles of TM/APC in septic DIC

	Functions	References
Lectin-like domain of TM	Inhibits HMGB1 (alarmins)	[63]
	Inhibits LPS (PAMPs)	[64]
	Inhibits adhesion of neutrophils to endothelial cells	[65]
	Inhibits complement factors	[70]
	Binds to thrombin	[33]
EGF-like domain of TM	Binds to thrombin	[33]
	Generates APC	[34,35,39]
	Protects vascular endothelial cells	[72]
	Inhibits complement factors	[68,69]
	Inhibits coagulation	[37,38]
	Enhances fibrinolysis by inhibition of PAI-1	[41]
APC	Activates G protein-coupled receptor and protects vascular endothelial cells	[43-47], [48,49]
	Increases Tie-2 and Ang1, and protects vascular endothelial cells	[51-54]
	Mitigates acute lung injury	[56]
	Binds to ApoER2 and activates prosurvival signals	[57,58]
	Binds to integrin receptors and inhibits inflammation	[59]
	Inhibits inflammation via inactivation of NF-κB	[60,61]
	Cleaves histones (DAMPs)

DIC, disseminated intravascular coagulation; TM, thrombomodulin; APC, activated protein C; HMGB1, high-mobility group box 1; PAMPs, pathogen-associated molecular patterns; DAMPs, damage-associated molecular patterns; PAI-1, plasminogen activator inhibitor-1; Tie2, tyrosine kinase with Ig-like loops and epidermal growth factor homology domains-2, Ang1, angiopoietin 1; ApoER2, apolipoprotein E receptor 2, NF-κB, nuclear factor-κ B.

ISSN: 2052-0492