title: Amidolytic, procoagulant, and activation-suppressing proteins produced by contact activation of blood factor XII in buffer solution.
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.
authors.affiliation: Department of Materials Science and Engineering, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Avantika
authors.initials: A
authors.lastname: Golas
authors.forename: Chyi-Huey Joshua
authors.initials: CH
authors.lastname: Yeh
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Siedlecki
authors.forename: Erwin A
authors.initials: EA
authors.lastname: Vogler
mesh_terms: D000577:Amides / Q000378:metabolism*; D001777:Blood Coagulation / Q000502:physiology*; D002021:Buffers; D005174:Factor XII / Q000378:metabolism*; D005898:Glass; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D012996:Solutions; D013499:Surface Properties; D013816:Thermodynamics; D014867:Water / Q000737:chemistry; D017155:Wettability
chemical_list: D000577:Amides; D002021:Buffers; D012996:Solutions; D014867:Water; D005174:Factor XII