Possible basis for the apparent surface selectivity of the contact activation of human blood coagulation factor XII

The activation of factor XII by the proteases factor XIIa and kallikrein is known to be greatly enhanced by certain negatively charged surfaces. Studies that compared factor XII surface binding to factor XII activation found that binding alone was insufficient to account for surface enhancement of the activation rate. The temperature dependence of the reaction showed unusual behavior that may be related to the conformational change of factor XII following binding; the rate of factor XII activation had a relatively low temperature optimum (0-47°C) that was sensitive to choice of surface and salt concentration. In temperature studies, below 47°C, the decrease in the activation rate was not related to the thermal denaturation of enzyme or substrate, nor to the choice of activator enzyme (factor XIIa or kallikrein), nor to the species of factor XII (human or bovine) but to a behavior, designated a thermal transition, associated with the surface or the protein-surface interaction. The previously reported surface selectivity of contact activation is possibly due to the temperature characteristics and other properties of the thermal transition; a surface that has a low-temperature thermal transition and that is highly sensitive to salt will be a "poor" contact surface under the usual choice of reaction conditions (∼ 150 mM ionic strength and 37°C). However, solution conditions were identified that allowed the following negatively charged surfaces to function, in nearly equal potency, in the activation of factor XII: phosphatidylserine, phosphatidylglycerol, phosphatidic acid, phosphatidylinositol 4-phosphate, heparin, and 5-kDa dextran sulfate, as well as the previously characterized sulfatide and 500-kDa dextran sulfate. The thermal transition may also explain the phenomenon of cold-promoted activation of plasma; plasma, or its storage containers, may contain "poor" contact surfaces that become active at low temperature. The surface property that is responsible for the thermal transition has not been identified but appears to account for several properties of contact activation.