Immobilized transition metal ions stimulate contact activation and drive factor XII-mediated coagulation
| Autor: | Nicola J. Mutch, Emily K. Waters, James H. Morrissey |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
inorganic chemicals
Kininogen High-Molecular-Weight Time Factors High-molecular-weight kininogen Metal ions in aqueous solution Oleic Acids Factor XIIa Article chemistry.chemical_compound Nickel Humans Blood Coagulation Factor XI Chelating Agents Phosphatidylethanolamine Factor XII Liposome Binding Sites Lysine Prekallikrein Succinates Hematology Phosphatidylserine Cobalt Surface Plasmon Resonance Enzyme Activation Zinc chemistry Coagulation Biochemistry Liposomes Biophysics Prothrombin Time Partial Thromboplastin Time Adsorption Copper |
| Zdroj: | Journal of thrombosis and haemostasis : JTH. 10(10) |
| ISSN: | 1538-7836 |
| Popis: | Summary. 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, Km and kcat 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text