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Competitive-protein adsorption in contact activation of blood factor XII ☆☆☆

Paper ID Volume ID Publish Year Pages File Format Full-Text
10739 701 2007 15 PDF Available
Title
Competitive-protein adsorption in contact activation of blood factor XII ☆☆☆
Abstract

Contact activation of blood factor XII (FXII, Hageman factor) is moderated by the protein composition of the fluid phase in which FXII is dissolved. Solution yield of FXIIa arising from FXII contact with hydrophilic activating particles (fully water-wettable glass) suspended in a protein cocktail is shown to be significantly greater than that obtained under corresponding activation conditions in buffer solutions containing only FXII. By contrast, solution yield of FXIIa arising from FXII contact with hydrophobic particles (silanized glass) suspended in protein cocktail is sharply lower than that obtained in buffer. This confirms that contact activation is not specific to anionic hydrophilic surfaces as proposed by the accepted biochemistry of surface activation. Rather, contact activation in the presence of proteins unrelated to the plasma coagulation cascade leads to an apparent specificity   for hydrophilic surfaces that is actually due to a relative diminution of activation at hydrophobic surfaces and an enhancement at hydrophilic surfaces. Furthermore, the rate of FXIIa accumulation in whole-plasma and buffer solution is found to decrease with time in the continuous presence of activating surfaces, leading to a steady-state FXIIa yield dependent on the initial FXII solution concentration for both hydrophilic and hydrophobic procoagulant particles suspended in either plasma, protein cocktail, or buffer. These results strongly suggest that activation competes with an autoinhibition reaction in which FXIIa itself inhibits FXII→FXIIa. Experimental results are modeled using a reaction scheme invoking FXII activation and autoinhibition linked to protein adsorption to procoagulant surfaces, where FXII activation is presumed to proceed by either autoactivation (FXII⟶surfaceFXIIa) and autohydrolysis (FXII⟶FXIIa2FXIIa) in buffer solution or autoactivation and reciprocal activation (kallikrein-mediated hydrolysis) in plasma. FXII adsorption competition with other proteins in the fluid phase is proposed to affect the balance of activation and autoinhibition, leading to the observed moderation of FXIIa yield.

Keywords
Blood coagulation; FXII; Hageman factor; Contact activation; Autoactivation; Protein adsorption
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Competitive-protein adsorption in contact activation of blood factor XII ☆☆☆
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 28, Issue 30, October 2007, Pages 4355–4369
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
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Any Questions? feel free to contact us