RRML - Reciprocal antagonism between inflammation and the protein C system

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Nr. 21(2)/2013 DOI:10.2478/rrlm-2013-0003

Reciprocal antagonism between inflammation and the protein C system

Mircea Cucuianu, Ioana Brudasca, Luminita Plesca, Gyorgy Bodizs, Dan Colhon, Andrei Cucuianu

Abstract:

Protein C is a vitamin K-dependent serine protease secreted by the hepatocytes as an inactive zymogen and activated by thrombin bound to endothelial thrombomodulin. An endothelial protein C receptor (EPCR) is involved in both activation and enhancement of protein C activity, resulting in proteolytic degradation of clot-ting factors Va and VIIIa, thereby providing an efficient anticoagulant mechanism. Evidence was also provided that proinflammatory cytokines would impair the endothelia-mediated activation and activity of the Protein C system by inducing an internalization and proteolytic degradation of thrombomodulin and by shedding EPCR from the surface of endothelial cells membrane. Clinical and experimental studies also emphasized that an inflammatory acute phase reaction is accompanied by a commuted hepatic protein synthesis leading to an in-crease of plasma fibrinogen, factor VIII:C and of α1 protease inhibitor, while the plasma level of protein C zymogen decrease. On the other hand infusions of activated protein C were reported to protect from a toxico-septic shock by exerting not only anticoagulant but also anti-inflammatory effects.

Keywords: Protein C,thrombomodulin,endothelial protein C receptor,inflammation-dependent depressive effects,thera-peutic approach with activated protein C

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Cucuianu M, Brudasca I, Plesca L, Bodizs G, Colhon D, Cucuianu A. Reciprocal antagonism between inflammation and the protein C system. Rev Romana Med Lab. 2013;21(2):129-33. DOI:10.2478/rrlm-2013-0003