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

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