Mouse recombinant protein C variants with enhanced membrane affinity and hyper‐anticoagulant activity in mouse plasma

Krisinger, Michael J.; Guo, Li Jun; Salvagno, Gian Luca; Guidi, Gian Cesare; Lippi, Giuseppe; Dahlbäck, Björn

doi:10.1111/j.1742-4658.2009.07371.x

Cited by 9 publications

(9 citation statements)

References 51 publications

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“…Citrated plasma, platelet poor, was used for the thrombin generation assay. The amount of thrombin formed in plasma/NP samples were monitored using the thrombin generation assay as previously described [25] with the following modifications. Natural phospholipids (PL), 20/20/60 PS:PE:PC, were prepared.…”

Section: Methodsmentioning

confidence: 99%

The nanoparticle protein corona formed in human blood or human blood fractions

Lundqvist

Augustsson

Lilja³

et al. 2017

PLoS ONE

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The protein corona formed around nanoparticles in protein-rich fluids plays an important role for nanoparticle biocompatibility, as found in several studies during the last decade. Biological fluids have complex compositions and the molecular components interact and function together in intricate networks. Therefore, the process to isolate blood or the preparation of blood derivatives may lead to differences in the composition of the identified protein corona around nanoparticles. Here, we show distinct differences in the protein corona formed in whole blood, whole blood with EDTA, plasma, or serum. Furthermore, the ratio between particle surface area to protein concentration influences the detected corona. We also show that the nanoparticle size per se influences the formed protein corona due to curvature effects. These results emphasize the need of investigating the formation and biological importance of the protein corona in the same environment as the nanoparticles are intended for or released into.

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Section: Methodsmentioning

confidence: 99%

The nanoparticle protein corona formed in human blood or human blood fractions

Lundqvist

Augustsson

Lilja³

et al. 2017

PLoS ONE

Self Cite

158

136

View full text Add to dashboard Cite

show abstract

“…The amount of thrombin formed in plasma/NP samples were monitored using the thrombin generation assay as previously described 18 with the following modifications. Natural phospholipids, 20/20/60 PS:PE:PC, were mixed and prepared.…”

Section: Thrombin Generation Assaymentioning

confidence: 99%

Polystyrene nanoparticles affecting blood coagulation

Oslakovic

Cedervall

Linse

et al. 2012

Nanomedicine: Nanotechnology, Biology and Medicine

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“…Liposomes were immobilized to a L1 sensor chip surfaces (GE Healthcare) using a Biacore T100 (Biacore) to a response of 5000 to 7000 response units, as previously described. 34 The presence of a procoagulant binding surface was confirmed by factor Xa association and dissociation, which both were predictably monoexponential. …”

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confidence: 95%

Activated protein C cofactor function of protein S: a novel role for a γ-carboxyglutamic acid residue

Ahnström

Andersson

Canis

et al. 2011

Blood

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Protein S has an important anticoagulant function by acting as a cofactor for activated protein C (APC). We recently reported that the EGF1 domain residue Asp95 is critical for APC cofactor function. In the present study, we examined whether additional interaction sites within the Gla domain of protein S might contribute to its APC cofactor function. We examined 4 residues, composing the previously reported "Face1" (N33S/P35T/ E36A/Y39V) variant, as single point substitutions. Of these protein S variants, protein S E36A was found to be almost completely inactive using calibrated automated thrombography. In factor Va inactivation assays, protein S E36A had 89% reduced cofactor activity compared with wild-type protein S and was almost completely inactive in factor VIIIa inactivation; phospholipid binding was, however, normal. Glu36 lies outside the -loop that mediates Ca 2؉ -dependent phospholipid binding. Using mass spectrometry, it was nevertheless confirmed that Glu36 is ␥-carboxylated. Our finding that Gla36 is important for APC cofactor function, but not for phospholipid binding, defines a novel function (other than Ca 2؉ coordination/phospholipid binding) for a Gla residue in vitamin K-dependent proteins. It also suggests that residues within the Gla and EGF1 domains of protein S act cooperatively for its APC cofactor function. (Blood. 2011;117(24):6685-6693) IntroductionProtein S is an anticoagulant plasma protein recognized as a member of the protein C anticoagulant pathway, in which it acts as a cofactor for activated protein C (APC). 1 Protein S mediates its APC cofactor activity by enhancing the inactivation of activated coagulation factors V (FVa) and VIII (FVIIIa). Protein S also inhibits thrombin generation independently of APC, which has recently been attributed to an enhancement of the activity of tissue factor pathway inhibitor (TFPI). 2,3 Numerous studies have shown an association between protein S deficiency and an increased risk for thrombosis. [4][5][6][7][8][9] The importance of protein S in vivo has been confirmed in mouse models where mice die in utero of coagulopathy and hemorrhages after knocking out the gene-encoding protein S (PROS1). 10,11 Protein S is a 635-amino acid vitamin K-dependent glycoprotein. It circulates in plasma at a concentration of 350nM, with approximately 60% being in complex with C4b-binding protein. 12 It has generally been accepted that only free protein S can mediate cofactor function for APC, 13,14 but this has recently been questioned by Maurissen et al who showed that the protein S-C4b-binding protein complex impairs APC-catalyzed proteolysis of FVa at Arg506, whereas it enhances the APC-catalyzed proteolysis at Arg306. 15 Protein S is divided into a number of structural domains composing an N-terminal vitamin K-dependent Gla domain, a thrombin-sensitive region (TSR), 4 epidermal growth factor (EGF)-like domains, and a region homologous to sex hormone binding globulin domain. 1,13 In vitamin K-dependent proteins, ␥-carboxylation of glutamic acid residues leadin...

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Mouse recombinant protein C variants with enhanced membrane affinity and hyper‐anticoagulant activity in mouse plasma

Cited by 9 publications

References 51 publications

The nanoparticle protein corona formed in human blood or human blood fractions

The nanoparticle protein corona formed in human blood or human blood fractions

Polystyrene nanoparticles affecting blood coagulation

Activated protein C cofactor function of protein S: a novel role for a γ-carboxyglutamic acid residue

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