Protein S: a conduit between anticoagulation and inflammation.

Abstract

OBJECTIVE:

To review the multifaceted roles of the anticoagulant protein S, facilitating a better comprehension of this protein's role in anticoagulation and inflammation pathways and the crosstalk between these pathologic states.

DATA SOURCES AND STUDY SELECTION:

Original research and review articles published in English pertaining to protein S, sourced from PubMed, during the last 30 yrs.

DATA EXTRACTION AND SYNTHESIS:

The protein C anticoagulant pathway is an essential mechanism for attenuating thrombin generation by the membrane-bound procoagulant complexes, tenase and prothrombinase. Protein S is a nonenzymatic protein. In the absence of activated protein C, it demonstrates anticoagulant activity; in the presence of activated protein C, it functions as a cofactor for activated protein C-dependent proteolytic inactivation of the coagulation cofactors factor Va and factor VIIIa. However, in plasma, these anticoagulant activities are limited by the concentration of free protein S (approximately 40% of the total protein S plasma concentration). The remaining protein S (approximately 60%) is found in a high-affinity, calcium-stabilized complex with C4b-binding protein, which renders this fraction devoid of anticoagulant function. Several recent investigations have attributed novel activated protein C-independent functions of protein S to the association of protein S with C4b-binding protein, thus establishing the importance of this fraction of plasma protein S.

CONCLUSIONS:

Together, these data support a role for protein S in both anticoagulation and inflammation, facilitating a better understanding of the need for both free and C4b-binding protein-bound protein S. Although these physiologic roles are truly dichotomous in terms of functional end point, mechanistically, both involve high-affinity membrane binding to phosphatidylserine-bearing surfaces. This binding is mediated by the n-terminal gamma-carboxyglutamic acid-rich domain of this protein.

• Authors: Alan C Rigby, Marianne A Grant
• Journal: Critical care medicine (Crit Care Med) Vol. 32 Issue 5 Suppl Pg. S336-41 (May 2004) ISSN: 0090-3493 [Print] United States
• PMID: 15118541 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Protein C
• Protein S

Topics

• Animals
• Blood Coagulation
• Humans
• Inflammation (immunology)
• Protein C (physiology)
• Protein S (physiology)