Factor XII-dependent contact activation on endothelial cells and binding proteins gC1qR and cytokeratin 1

Although proteins of the kinin-forming pathway are bound along the surface of endothelial cells, the mechanism of activation of this proteolytic casca de is unclear. Endothelial cell surface proteins, gClqR and cytokeratin 1, are capable of binding Factor XII and high molecular weight kininogen (HK) in a zinc-dependent reaction thus we considered the possibility that these proteins might catalyze initiation of the cascade. Incubation of Factor XII , prekallikrein, and HK with gClqR or cytokeratin 1 leads to a zinc-depende nt and Factor XII-dependent conversion of prekallikrein to kallikrein. We a lso demonstrate that normal plasma is capable of activating upon interactio n with the cells whereas plasma deficient in Factor XII, prekallikrein and HK do not activate. Normal plasma activation was inhibitable by antibody to gClqR and cytokeratin 1, Thus, gClqR and cytokeratin 1, represent potentia l initiating surfaces for activation of the plasma kinin-forming cascade an d may do so as a result of their expression along cell surfaces.