Activation of the kinin-forming cascade on the surface of endothelial cells

Activation of the plasma kallikrein-kinin forming cascade takes place upon incubation with human umbilical vein endothelial cells. The mechanism by wh ich initiation occurs is uncertain. Zinc-dependent binding of plasma protei ns to gC1qR, cytokeratin 1, and perhaps u-PAR is requisite for activation t o take place. We demonstrate here that during a 2 hour incubation time plas ma deficient in either factor XII or high molecular weight kininogen (HK) f ails to activate, as compared to normal plasma, but with more prolonged inc ubation, factor XII-deficient plasma gradually activates while HK-deficient plasma does not. Our data support both factor XII-dependent (rapid) and fa ctor XII-independent (slow) mechanisms; the latter may require a cell-deriv ed protease to activate prekallikrein and the presence of zinc ions and HK.