Familial protein S deficiency is associated with recurrent thrombosis.

Nixon, Randal R.; Cooper, M. Robert; Esmon, CT

doi:10.1172/jci111632

Cited by 623 publications

(282 citation statements)

References 19 publications

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“…Protein S functions as cofactor to apc in the degradation of factors Va and VIIIa (17,18). The importance of protein C and protein S is demonstrated by the fact that deficiency of either is associated with increased risk of thrombosis (19,20). Because anionic membrane surfaces (such as that provided by activated platelets) have been shown to be equally competent in promoting proand anticoagulant reactions (21,22), it is likely that the surface of apoptotic cells is also able to promote anticoagulant reactions.…”

mentioning

confidence: 99%

Vitamin K-Dependent Protein S Localizing Complement Regulator C4b-Binding Protein to the Surface of Apoptotic Cells

Webb

Blom

Dahlbäck

2002

The Journal of Immunology

103

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Apoptosis is characterized by a lack of inflammatory reaction in surrounding tissues, suggesting local control of complement activation. During the initial stage of apoptosis, cells expose negatively charged phospholipid phosphatidylserine on their surfaces. The vitamin K-dependent protein S has a high affinity for this type of phospholipid. In human plasma, 60–70% of protein S circulates in complex with C4b-binding protein (C4BP). The reason why protein S and C4BP form a high-affinity complex in plasma is not known. However, C4BP is an important regulator of the classical pathway of the complement system where it acts as a cofactor in degradation of complement protein C4b. Using Jurkat cells as a model system for apoptosis, we now show protein S to bind to apoptotic cells. We further demonstrate protein S-mediated binding of C4BP to apoptotic cells. Binding of the C4BP-protein S complex to apoptotic cells was calcium-dependent and could be blocked with Abs directed against the phospholipid-binding domain in protein S. Annexin V, which binds to exposed phosphatidylserine on the apoptotic cell surface, could inhibit the binding of protein S. The C4BP that was bound via protein S to the apoptotic cells was able to interact with the complement protein C4b, supporting a physiological role of the C4BP/protein S complex in regulation of complement on the surface of apoptotic cells.

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mentioning

confidence: 99%

Vitamin K-Dependent Protein S Localizing Complement Regulator C4b-Binding Protein to the Surface of Apoptotic Cells

Webb

Blom

Dahlbäck

2002

The Journal of Immunology

103

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“…Proteolytic inactivation of FVa by activated protein C (APC) is an essential reaction in the anticoagulant protein C pathway (6), which is important in the regulation of thrombin formation and in the inhibition of acute inflammation triggered by coagulation (7). Congenital deficiencies in this pathway are associated with thrombotic disease (8,9). Inactivation of FVa activity by APC is associated with cleavage of three peptide bonds in the heavy chain of FVa, which have been localized at Arg-306, Arg-506, and Arg-679 (10).…”

Section: Human Blood Coagulation Factor V (Fv)mentioning

confidence: 99%

Factor Va Is Inactivated by Activated Protein C in the Absence of Cleavage Sites at Arg-306, Arg-506, and Arg-679

Kolfschoten

Dirven

Vos

et al. 2004

Journal of Biological Chemistry

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“…8 The coagulation inhibitors with deficiencies that associate with thrombophilia include antithrombin, protein S, and protein C (PC). [9][10][11] Many different mutations produce PC deficiency, with a combined prevalence of 0.3%. 12 Although at increased risk of VT, especially in penetrant families, 13 most PC-deficient persons are asymptomatic.…”

Section: Introductionmentioning

confidence: 99%