Article

Surface-energy dependent contact activation of blood factor XII

Department of Bioengineering, The Pennsylvania State University, University Park, PA 16802, USA.
Biomaterials (Impact Factor: 8.31). 11/2009; 31(6):1068-79. DOI: 10.1016/j.biomaterials.2009.10.039
Source: PubMed

ABSTRACT Contact activation of blood factor XII (FXII, Hageman factor) in neat-buffer solution exhibits a parabolic profile when scaled as a function of silanized-glass-particle activator surface energy (measured as advancing water adhesion tension tau(a)(o)=gamma(lv)(o)cos theta in dyne/cm, where gamma(lv)(o) is water interfacial tension in dyne/cm and theta is the advancing contact angle). Nearly equal activation is observed at the extremes of activator water-wetting properties -36<tau(a)(o)<72 dyne/cm (0 degrees <or=theta<120 degrees), falling sharply through a broad minimum within the 20<tau(a)(o)<40 dyne/cm (55 degrees <theta<75 degrees) range over which activation yield (putatively FXIIa) rises just above detection limits. Activation is very rapid upon contact with all activators tested and did not significantly vary over 30 min of continuous FXII-procoagulant contact. Results suggest that materials falling within the 20<tau(a)(o)<40 dyne/cm surface-energy range should exhibit minimal activation of blood-plasma coagulation through the intrinsic pathway. Surface chemistries falling within this range are, however, a perplexingly difficult target for surface engineering because of the critical balance that must be struck between hydrophobicity and hydrophilicity. Results are interpreted within the context of blood plasma coagulation and the role of water and proteins at procoagulant surfaces.

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    • "Perhaps a more important consideration is that the effects of collagen on the activities of the proteins tested indicate that studies with biomaterials should consider such reactions as part of their screening for biocompatibility, especially as high local concentrations of collagen would likely be present in such materials. Thus we would suggest that all materials that use collagen (especially type IV) should be evaluated not only for their thrombogenic potential, but also for more specific actions on the contact system proteinases and C1-inhibitor, such as have been carried out with other biomaterials [5, 6, 19–21]. "
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    ABSTRACT: The contact system of coagulation can be activated when in contact with biomaterials. As collagen is being tested in novel biomaterials in this study, we have investigated how type IV collagen affects plasma kallikrein and C1-inhibitor. Firstly, we showed C1-inhibitor binds to type IV collagen with a Kd of 0.86 μM. The effects of type IV collagen on plasma kallikrein, factor XIIa, and β-factor XIIa activity and on C1-inhibitor function were determined. Factor XIIa rapidly lost activity in the presence of type IV collagen, whereas plasma kallikrein and β-factor XIIa were more stable. The rate of inhibition of plasma kallikrein by C1-inhibitor was decreased by type IV collagen in a dose-dependent manner. These studies could be relevant to the properties of biomaterials, which contain collagen, and should be considered in the testing for biocompatibility.
    International Journal of Biomaterials 02/2012; 2012:212417. DOI:10.1155/2012/212417
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    • "Our investigations into contact activation of plasma coagulation have revealed that the first step of the coagulation cascade, activation of the zymogen FXII into the protease form FXIIa, is moderated by the protein composition of the fluid phase in which FXII is dissolved [17] [18]. This surface-catalyzed reaction is sometimes referred to as autoactivation ðFXII/ activator surface FXIIaÞ and may produce other proteases such as FXIIf that also exhibit procoagulant properties [16] [17]. Autoactivation of FXII in pure buffer solution generates a parabolic yield of procoagulant enzymes (putatively FXIIa) as a function of activator hydrophilicity , high at both hydrophobic and hydrophilic extremes of the wetting continuum but falling through a broad minimum between these extremes. "
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    ABSTRACT: Sepharose ion-exchange particles bearing strong Lewis acid/base functional groups (sulfopropyl, carboxymethyl, quaternary ammonium, dimethyl aminoethyl, and iminodiacetic acid) exhibiting high plasma protein adsorbent capacities are shown to be more efficient activators of blood factor XII in neat-buffer solution than either hydrophilic clean-glass particles or hydrophobic octyl sepharose particles (FXII (activator)→(surface) FXIIa; a.k.a autoactivation, where FXII is the zymogen and FXIIa is a procoagulant protease). In sharp contrast to the clean-glass standard of comparison, ion-exchange activators are shown to be inefficient activators of blood plasma coagulation. These contrasting activation properties are proposed to be due to the moderating effect of plasma-protein adsorption on plasma coagulation. Efficient adsorption of blood-plasma proteins unrelated to the coagulation cascade impedes FXII contacts with ion-exchange particles immersed in plasma, reducing autoactivation, and causing sluggish plasma coagulation. By contrast, plasma proteins do not adsorb to hydrophilic clean glass and efficient autoactivation leads directly to efficient activation of plasma coagulation. It is also shown that competitive-protein adsorption can displace FXIIa adsorbed to the surface of ion-exchange resins. As a consequence of highly-efficient autoactivation and FXIIa displacement by plasma proteins, ion-exchange particles are slightly more efficient activators of plasma coagulation than hydrophobic octyl sepharose particles that do not bear strong Lewis acid/base surface functionalities but to which plasma proteins adsorb efficiently. Plasma proteins thus play a dual role in moderating contact activation of the plasma coagulation cascade. The principal role is impeding FXII contact with activating surfaces, but this same effect can displace FXIIa from an activating surface into solution where the protease can potentiate subsequent steps of the plasma coagulation cascade.
    Biomaterials 01/2012; 33(1):9-19. DOI:10.1016/j.biomaterials.2011.09.034 · 8.31 Impact Factor
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    • "Particles were further mixed in suspension with PBS before use in activation experiments described below. A hypothetical " equivalent wetting' parameter was calculated using a linear combining rule as described previously [2] "
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    ABSTRACT: The relative proportions of enzymes with amidolytic or procoagulant activity produced by contact activation of the blood zymogen factor XII (FXII, Hageman factor) in buffer solution depends on activator surface chemistry/energy. As a consequence, chromogenic assay of amidolytic activity (cleavage of amino acid bonds in s-2302 chromogen) does not correlate with the traditional plasma coagulation time assay for procoagulant activity (protease activity inducing clotting of blood plasma). Amidolytic activity did not vary significantly with activator particle surface energy, herein measured as water adhesion tension τ(o)=γ(lv)(o)cosθ(a) ; where γ(lv)(o) is pure buffer interfacial tension and θ(a) is the advancing contact angle. By contrast, procoagulant activity varied as a parabolic-like function of τ(o), high at both hydrophobic and hydrophilic extremes of activator surface energy and falling through a broad minimum within a 20<τ(o)<40 mJ/m(2) (55°<θ(a) < 75°) range, corroborating and expanding previously-published work. It is inferred from these functional assays that an unknown number of protein fragments are produced by contact activation of FXII (a.k.a. autoactivation) rather than just αFXIIa and βFXIIa as popularly believed. Autoactivation products produced by activator particles within the 20<τ(o)<40 mJ/m(2) (55°<θ(a) < 75°) surface-energy range suppresses production of procoagulant enzymes by activators selected from the hydrophobic or hydrophilic surface-energy extremes through as-yet unknown biophysical chemistry. Suppression proteins may be responsible for the experimentally-observed autoinhibition of the autoactivation reaction.
    Biomaterials 09/2011; 32(36):9747-57. DOI:10.1016/j.biomaterials.2011.09.020 · 8.31 Impact Factor
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