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 which initiation occurs is uncertain. Zinc-dependent binding of plasma proteins to gC1qR, cytokeratin 1, and perhaps u-PAR is requisite for activation to take place. We demonstrate here that during a 2 hour incubation time plasma deficient in either factor XII or high molecular weight kininogen (HK) fails to activate, as compared to normal plasma, but with more prolonged incubation, factor XII-deficient plasma gradually activates while HK-deficient plasma does not. Our data support both factor XII-dependent (rapid) and factor XII-independent (slow) mechanisms; the latter may require a cell-derived protease to activate prekallikrein and the presence of zinc ions and HK.
Department of Medicine, and the Konishi-MUSC Institute for Inflammation Research, Medical University of South Carolina, Charleston 29425, USA.
K
K
Joseph
B
B
Ghebrehiwet
A P
AP
Kaplan
D019138:Antibodies, Blocking / Q000494:pharmacology; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005174:Factor XII / Q000494:pharmacology; D006801:Humans; D007704:Kininogens / Q000494:pharmacology; D007705:Kinins / Q000096:biosynthesis* / Q000502:physiology; D008970:Molecular Weight; D011288:Prekallikrein / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism
D019138:Antibodies, Blocking; D007704:Kininogens; D007705:Kinins; D011956:Receptors, Cell Surface; D005174:Factor XII; D011288:Prekallikrein