Binding of activated Factor XII to endothelial cells affects its inactivation by the C1‐esterase inhibitor

I Schousboe - European journal of biochemistry, 2003 - Wiley Online Library
I Schousboe
European journal of biochemistry, 2003Wiley Online Library
It is well known that activated Factor XII (FXIIa) and kallikrein are rapidly inactivated in
plasma as a result of reaction with endogenous inhibitors. The purpose of this may be to
prevent uncontrolled deleterious spreading and activation of target zymogens. Both FXII and
the complex plasma prekallikrein/high molecular mass kininogen become activated when
they bind, in a Zn2+‐dependent manner, to receptors on human umbilical vein endothelial
cells (HUVEC). The C1‐esterase inhibitor (C1‐INH) is by far the most efficient inhibitor of …
It is well known that activated Factor XII (FXIIa) and kallikrein are rapidly inactivated in plasma as a result of reaction with endogenous inhibitors. The purpose of this may be to prevent uncontrolled deleterious spreading and activation of target zymogens. Both FXII and the complex plasma prekallikrein/high molecular mass kininogen become activated when they bind, in a Zn2+‐dependent manner, to receptors on human umbilical vein endothelial cells (HUVEC). The C1‐esterase inhibitor (C1‐INH) is by far the most efficient inhibitor of FXIIa. In the present study it has been investigated whether binding of FXIIa to HUVEC might offer protection against inactivation by C1‐INH. It appeared that the relative amidolytic activity of purified FXIIa bound to the surface of HUVEC decreased according to the concentration of C1‐INH in medium; however, the decrease was smaller than that measured for inactivation of FXIIa in solution. The secondary rate constant for the inactivation was 3–10‐fold lower for cell‐bound than for soluble FXIIa. The inactivation was found to be caused by C1‐INH binding to cell‐bound FXIIa. Accordingly, the amidolytic activity of saturated amounts of cell‐bound FXIIa was reduced in the presence of C1‐INH and was theoretically nonexistent at physiological C1‐INH concentrations. Amidolytic activity was, however, present on HUVEC incubated with plasma indicating that the endogenous C1‐INH did not completely abolish the activity of FXIIa generated during the incubation period. This supports the hypothesis that binding to endothelial cells protects the activated FXII against inactivation by its major endogenous inhibitor. Hence, the function of FXII may be localized at cellular surfaces.
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