Thrombomodulin and protein C activation at the microcirculatory level

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Taken from "Bench-to-bedside review: Endothelial cell dysfunction in severe sepsis: a role in organ dysfunction?"

Critical Care 2003;7(2):130-138.

Published online 6 Jan 2003

PMCID:PMC270612.

Copyright © 2003 BioMed Central Ltd

The endothelial cell surface thrombin (Th)-binding protein thrombomodulin (TM) is responsible for inhibition of thrombin activity. TM, when bound to Th, forms a potent protein C activator complex. Loss of TM and/or internalization results in Th-thrombin receptor (TR) interaction. Loss of TM and associated protein C activation represents the key event of decreased endothelial coagulation modulation ability and increased inflammation pathways. Adapted from Iba and coworkers []. ATIII, antithrombin III; NF-κ, nuclear factor-κB; PAI, plasminogen activator inhibitor; Th, thrombin; TM, thrombomodulin.