title: Activation of the plasma kallikrein/kinin system on endothelial cell membranes.
abstract: For more than three decades, it has been known that the plasma kallikrein/kinin system becomes activated when exposed to artificial, negatively charged surfaces. The existence of an encompassing in vivo, negatively charged surface capable of activation of the plasma kallikrein/kinin system has, however, never been convincingly demonstrated. In this report, we describe current knowledge on how the proteins of the plasma kallikrein/kinin system assemble to become activated on cell membranes. On endothelial cells, the activation of the plasma kallikrein/kinin system is not initiated by factor XII autoactivation as seen on artificial surfaces. On endothelial cells, prekallikrein is activated by an antipain sensitive protease. Prekallikrein activation 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 formed on endothelial cell membranes is capable of cleaving its receptor and native substrate, high molecular weight kininogen, liberating bradykinin and the HK PK complex from the endothelial cell surface. Endothelial cell-associated kallikrein also is capable of kinetically favorable pro-urokinase and, subsequent, plasminogen activation.
authors.affiliation: Institute for Medical Biochemistry and Genetics, University of Copenhagen, Denmark.
authors.forename: R
authors.initials: R
authors.lastname: Røjkjaer
authors.forename: A H
authors.initials: AH
authors.lastname: Schmaier
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005174:Factor XII / Q000502:physiology; D005342:Fibrinolysis; D006801:Humans; D016234:Kallikrein-Kinin System / Q000502:physiology*; D007705:Kinins / Q000378:metabolism*; D020842:Plasma Kallikrein / Q000378:metabolism*; D011288:Prekallikrein / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology
chemical_list: D007705:Kinins; D005174:Factor XII; D011288:Prekallikrein; D020842:Plasma Kallikrein; D015032:Zinc