TY - JOUR
T1 - Competitive-protein adsorption in contact activation of blood factor XII
AU - Zhuo, Rui
AU - Siedlecki, Christopher
AU - Vogler, Erwin A.
N1 - Funding Information:
This work was supported, in part, by the National Institute of Health PHS 2R01HL069965. Authors appreciate additional support from the Materials Research Institute and Departments of Bioengineering and Materials Science and Engineering, Penn State University.
PY - 2007/10
Y1 - 2007/10
N2 - 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 over({long rightwards arrow}, surface) FXIIa) and autohydrolysis (FXII over({long rightwards arrow}, FXIIa) 2 FXIIa) 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.
AB - 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 over({long rightwards arrow}, surface) FXIIa) and autohydrolysis (FXII over({long rightwards arrow}, FXIIa) 2 FXIIa) 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.
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U2 - 10.1016/j.biomaterials.2007.06.019
DO - 10.1016/j.biomaterials.2007.06.019
M3 - Article
C2 - 17644174
AN - SCOPUS:34547693092
SN - 0142-9612
VL - 28
SP - 4355
EP - 4369
JO - Biomaterials
JF - Biomaterials
IS - 30
ER -