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 cascade is unclear. Endothelial cell surface proteins, gC1qR 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 gC1qR or cytokeratin 1 leads to a zinc-dependent and Factor XII-dependent conversion of prekallikrein to kallikrein. We also demonstrate that normal plasma is capable of activating upon interaction with the cells whereas plasma deficient in Factor XII, prekallikrein and HK do not activate. Normal plasma activation was inhibitable by antibody to gC1qR and cytokeratin 1. Thus, gC1qR and cytokeratin 1, represent potential initiating surfaces for activation of the plasma kinin-forming cascade and may do so as a result of their expression along cell surfaces.
Joseph
K
K
Department of Medicine and Konishi-MUSC Institute for Inflammation Research, Medical University of South Carolina, Charleston 29425, USA.
Shibayama
Y
Y
Ghebrehiwet
B
B
Kaplan
A P
AP
D002352:Carrier Proteins; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D005174:Factor XII / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D018960:Hyaluronan Receptors; D016234:Kallikrein-Kinin System / Q000187:drug effects*; D007633:Keratins / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D019679:Kininogen, High-Molecular-Weight / Q000494:pharmacology; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones / Q000378:metabolism / Q000494:pharmacology; D011288:Prekallikrein / Q000378:metabolism / Q000494:pharmacology; D011951:Receptors, Complement / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology; D015032:Zinc / Q000494:pharmacology
C087299:C1QBP protein, human; D002352:Carrier Proteins; D003174:Complement C1 Inactivator Proteins; D018960:Hyaluronan Receptors; D019679:Kininogen, High-Molecular-Weight; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D011951:Receptors, Complement; C032402:complement 1q receptor; D007633:Keratins; D005174:Factor XII; D011288:Prekallikrein; D015032:Zinc