Activation of the plasma kallikrein/kinin system on endothelial cell membranes

For more than three decades, it has been known that the plasma kallikrein/k inin system becomes activated when exposed to artificial, negatively charge d surfaces. The existence of an encompassing in vivo, negatively charged su rface capable of activation of the plasma kallikrein/kinin system has, howe ver, never been convincingly demonstrated. in this report, we describe curr ent knowledge on how the proteins of the plasma kallikrein/kinin system ass emble to become activated on cell membranes. On endothelial cells, the acti vation of the plasma kallikrein/kinin system is not initiated by factor XII autoactivation as seen on artificial surfaces. On endothelial cells, preka llikrein is activated by an antipain sensitive protease. Prekallikrein acti vation is dependent on the presence of high molecular weight kininogen and an optimal free Zn2+ concentration, Kallikrein generated on the surface of endothelial cell is capable of activating factor XII. Further, kallikrein f ormed on endothelial cell membranes is capable of cleaving its receptor and native substrate, high molecular weight kininogen, liberating bradykinin a nd the HK.PK complex from the endothelial cell surface. Endothelial cell-as sociated kallikrein also is capable of kinetically favorable pro-urokinase and, subsequent, plasminogen activation. (C) 1999 Elsevier Science B.V. All rights reserved.