Signal transduction induced by activated protein C: no role in protection against sepsis?
The anticoagulant activated protein C (APC) is historically known as a risk factor for venous thrombosis. However, after the positive results of the protein C worldwide evaluation in severe sepsis (PROWESS) trial, which showed that APC was the first drug that considerably reduced sepsis-related mortality, APC is considered a pleiotropic protein with both anticoagulant and anti-inflammatory properties. In addition, in vitro studies have suggested that APC-induced intracellular signal transduction is a potential mechanism by which APC might be protective against sepsis. Recently, however, the efficacy of APC in sepsis has been argued, and also the extent to which the signal transduction capacity of APC contributes to its pro-survival effects is debated. Here, we review the role of APC in the body natural defense against sepsis and discuss the mechanism by which APC might act at a cellular level.
Slofstra
Sjoukje H
SH
Center for Experimental and Molecular Medicine, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands.
ten Cate
Hugo
H
Spek
C Arnold
CA
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D006801:Humans; D008954:Models, Biological; D011486:Protein C / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D018805:Sepsis / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000925:Anticoagulants; D011486:Protein C