Departments of Materials Science and Engineering, The Pennsylvania State University, University Park, PA 16802, USA.
Biomaterials. 2012 Jan;33(1):9-19. doi: 10.1016/j.biomaterials.2011.09.034. Epub 2011 Oct 6.
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.
载有强路易斯酸碱功能基团（磺丙基、羧甲基、季铵、二甲基氨基乙基和亚氨基二乙酸）的琼脂糖离子交换颗粒具有很高的血浆蛋白吸附能力，与亲水性清洁玻璃颗粒或疏水性辛基琼脂糖颗粒相比，在纯缓冲溶液中更有效地激活血液因子 XII（FXII（激活剂）→（表面）FXIIa；也称为自动激活，其中 FXII 是酶原，FXIIa 是促凝血酶）。与清洁玻璃标准形成鲜明对比的是，离子交换激活剂被证明是低效的血液凝固激活剂。这些对比鲜明的激活特性被认为是由于血浆蛋白吸附对血浆凝固的调节作用。与凝血级联无关的血液血浆蛋白的有效吸附会阻碍 FXII 与沉浸在血浆中的离子交换颗粒接触，从而减少自动激活，并导致血浆凝固缓慢。相比之下，血浆蛋白不会吸附到亲水性清洁玻璃上，有效的自动激活直接导致有效的血浆凝固激活。还表明，竞争蛋白吸附可以取代吸附在离子交换树脂表面的 FXIIa。由于高效的自动激活和血浆蛋白对 FXIIa 的置换，离子交换颗粒比不具有强路易斯酸碱表面功能基团但能有效吸附血浆蛋白的疏水性辛基琼脂糖颗粒略有效地激活血浆凝固。因此，血浆蛋白在调节血浆凝固级联的接触激活中起着双重作用。主要作用是阻碍 FXII 与激活表面接触，但这种相同的效果可以将 FXIIa 从激活表面置换到溶液中，蛋白酶可以增强血浆凝固级联的后续步骤。
