Immobilized transition metal ions stimulate contact activation and drive factor XII-mediated coagulation

N. J. Mutch, E. K. Waters, J. H. Morrissey

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

. Background: Upon contact with an appropriate surface, factor XII (FXII) undergoes autoactivation or cleavage by kallikrein. Zn2+ is known to facilitate binding of FXII and the cofactor, high molecular weight kininogen (HK), to anionic surfaces. Objectives: To investigate whether transition metal ions immobilized on liposome surfaces can initiate coagulation via the contact pathway. Methods and results: Liposomes containing a metal ion-chelating lipid, 1,2-dioleoyl-sn-glycero-3-{(N[5-amino-1-carboxypentyl]iminodiacetic acid)succinyl} ammonium salt (DOGS-NTA), were prepared by membrane extrusion (20% DOGS-NTA, 40% phosphatidylcholine, 10% phosphatidylserine, and 30% phosphatidylethanolamine). Ni2+ immobilized on such liposomes accelerated clotting in normal plasma, but not factor XI (FXI)-deficient or FXII-deficient plasma. The results were similar to those obtained with a commercial activated partial thromboplastin time reagent. Charging such liposomes with other transition metal ions revealed differences in their procoagulant capacity, with Ni2+ > Cu2+ > Co2+ and Zn2+. Plasma could be depleted of FXI, FXII and HK by adsorption with Ni2+-containing beads, resulting in longer clot times. Consistent with this, FXI, FXII and HK bound to immobilized Ni2+ or Cu2+ with high affinity as determined by surface plasmon resonance. In the presence of Ni2+-bearing liposomes, K-m and k(cat) values derived for autoactivation of FXII and prekallikrein, as well as for activation of FXII by kallikrein or prekallikrein by FXIIa, were similar to literature values obtained in the presence of dextran sulfate. Conclusions: Immobilized Ni2+ and Cu2+ bind FXII, FXI and HK with high affinity and stimulate activation of the contact pathway, driving FXII-mediated coagulation. Activation of the contact system by immobilized transition metal ions may have implications during pathogenic infection or in individuals exposed to high levels of pollution.

Original languageEnglish
Pages (from-to)2108-2115
Number of pages8
JournalJournal of Thrombosis and Haemostasis
Volume10
Issue number10
DOIs
Publication statusPublished - Oct 2012

Keywords

  • coagulation
  • contact pathway
  • factor XI
  • factor XII
  • metal ions
  • thrombin

Cite this

Immobilized transition metal ions stimulate contact activation and drive factor XII-mediated coagulation. / Mutch, N. J.; Waters, E. K.; Morrissey, J. H.

In: Journal of Thrombosis and Haemostasis, Vol. 10, No. 10, 10.2012, p. 2108-2115.

Research output: Contribution to journalArticle

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abstract = ". Background: Upon contact with an appropriate surface, factor XII (FXII) undergoes autoactivation or cleavage by kallikrein. Zn2+ is known to facilitate binding of FXII and the cofactor, high molecular weight kininogen (HK), to anionic surfaces. Objectives: To investigate whether transition metal ions immobilized on liposome surfaces can initiate coagulation via the contact pathway. Methods and results: Liposomes containing a metal ion-chelating lipid, 1,2-dioleoyl-sn-glycero-3-{(N[5-amino-1-carboxypentyl]iminodiacetic acid)succinyl} ammonium salt (DOGS-NTA), were prepared by membrane extrusion (20{\%} DOGS-NTA, 40{\%} phosphatidylcholine, 10{\%} phosphatidylserine, and 30{\%} phosphatidylethanolamine). Ni2+ immobilized on such liposomes accelerated clotting in normal plasma, but not factor XI (FXI)-deficient or FXII-deficient plasma. The results were similar to those obtained with a commercial activated partial thromboplastin time reagent. Charging such liposomes with other transition metal ions revealed differences in their procoagulant capacity, with Ni2+ > Cu2+ > Co2+ and Zn2+. Plasma could be depleted of FXI, FXII and HK by adsorption with Ni2+-containing beads, resulting in longer clot times. Consistent with this, FXI, FXII and HK bound to immobilized Ni2+ or Cu2+ with high affinity as determined by surface plasmon resonance. In the presence of Ni2+-bearing liposomes, K-m and k(cat) values derived for autoactivation of FXII and prekallikrein, as well as for activation of FXII by kallikrein or prekallikrein by FXIIa, were similar to literature values obtained in the presence of dextran sulfate. Conclusions: Immobilized Ni2+ and Cu2+ bind FXII, FXI and HK with high affinity and stimulate activation of the contact pathway, driving FXII-mediated coagulation. Activation of the contact system by immobilized transition metal ions may have implications during pathogenic infection or in individuals exposed to high levels of pollution.",
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T1 - Immobilized transition metal ions stimulate contact activation and drive factor XII-mediated coagulation

AU - Mutch, N. J.

AU - Waters, E. K.

AU - Morrissey, J. H.

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N2 - . Background: Upon contact with an appropriate surface, factor XII (FXII) undergoes autoactivation or cleavage by kallikrein. Zn2+ is known to facilitate binding of FXII and the cofactor, high molecular weight kininogen (HK), to anionic surfaces. Objectives: To investigate whether transition metal ions immobilized on liposome surfaces can initiate coagulation via the contact pathway. Methods and results: Liposomes containing a metal ion-chelating lipid, 1,2-dioleoyl-sn-glycero-3-{(N[5-amino-1-carboxypentyl]iminodiacetic acid)succinyl} ammonium salt (DOGS-NTA), were prepared by membrane extrusion (20% DOGS-NTA, 40% phosphatidylcholine, 10% phosphatidylserine, and 30% phosphatidylethanolamine). Ni2+ immobilized on such liposomes accelerated clotting in normal plasma, but not factor XI (FXI)-deficient or FXII-deficient plasma. The results were similar to those obtained with a commercial activated partial thromboplastin time reagent. Charging such liposomes with other transition metal ions revealed differences in their procoagulant capacity, with Ni2+ > Cu2+ > Co2+ and Zn2+. Plasma could be depleted of FXI, FXII and HK by adsorption with Ni2+-containing beads, resulting in longer clot times. Consistent with this, FXI, FXII and HK bound to immobilized Ni2+ or Cu2+ with high affinity as determined by surface plasmon resonance. In the presence of Ni2+-bearing liposomes, K-m and k(cat) values derived for autoactivation of FXII and prekallikrein, as well as for activation of FXII by kallikrein or prekallikrein by FXIIa, were similar to literature values obtained in the presence of dextran sulfate. Conclusions: Immobilized Ni2+ and Cu2+ bind FXII, FXI and HK with high affinity and stimulate activation of the contact pathway, driving FXII-mediated coagulation. Activation of the contact system by immobilized transition metal ions may have implications during pathogenic infection or in individuals exposed to high levels of pollution.

AB - . Background: Upon contact with an appropriate surface, factor XII (FXII) undergoes autoactivation or cleavage by kallikrein. Zn2+ is known to facilitate binding of FXII and the cofactor, high molecular weight kininogen (HK), to anionic surfaces. Objectives: To investigate whether transition metal ions immobilized on liposome surfaces can initiate coagulation via the contact pathway. Methods and results: Liposomes containing a metal ion-chelating lipid, 1,2-dioleoyl-sn-glycero-3-{(N[5-amino-1-carboxypentyl]iminodiacetic acid)succinyl} ammonium salt (DOGS-NTA), were prepared by membrane extrusion (20% DOGS-NTA, 40% phosphatidylcholine, 10% phosphatidylserine, and 30% phosphatidylethanolamine). Ni2+ immobilized on such liposomes accelerated clotting in normal plasma, but not factor XI (FXI)-deficient or FXII-deficient plasma. The results were similar to those obtained with a commercial activated partial thromboplastin time reagent. Charging such liposomes with other transition metal ions revealed differences in their procoagulant capacity, with Ni2+ > Cu2+ > Co2+ and Zn2+. Plasma could be depleted of FXI, FXII and HK by adsorption with Ni2+-containing beads, resulting in longer clot times. Consistent with this, FXI, FXII and HK bound to immobilized Ni2+ or Cu2+ with high affinity as determined by surface plasmon resonance. In the presence of Ni2+-bearing liposomes, K-m and k(cat) values derived for autoactivation of FXII and prekallikrein, as well as for activation of FXII by kallikrein or prekallikrein by FXIIa, were similar to literature values obtained in the presence of dextran sulfate. Conclusions: Immobilized Ni2+ and Cu2+ bind FXII, FXI and HK with high affinity and stimulate activation of the contact pathway, driving FXII-mediated coagulation. Activation of the contact system by immobilized transition metal ions may have implications during pathogenic infection or in individuals exposed to high levels of pollution.

KW - coagulation

KW - contact pathway

KW - factor XI

KW - factor XII

KW - metal ions

KW - thrombin

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DO - 10.1111/j.1538-7836.2012.04890.x

M3 - Article

VL - 10

SP - 2108

EP - 2115

JO - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

SN - 1538-7933

IS - 10

ER -