Activation of the plasma kinin forming cascade along cell surfaces.
Proteins of the plasma kinin-forming cascade bind to endothelial cells and activation of the cascade can be initiated along the surface. The light chain of high molecular weight kininogen (HK) (domain 5) and factor XII bind to gC1qR, the heavy chain of HK (domain 3) binds to cytokeratin 1 and the interactions are zinc dependent. Prekallikrein binds to domain 6 of HK. Antisera to gC1qR and cytokeratin 1 inhibit binding and activation. Incubation of normal plasma with endothelial cells leads to gradual conversion of prekallikrein to kallikrein, while plasma deficient in factor XII or HK are inactive within a 2-hour time frame. Thus factor XII is critical for activation to proceed. Augmentation of these reactions may occur when C1 inhibitor is functionally deficient or with ACE inhibitors which also inhibit kininases.
Kaplan
A P
AP
Department of Medicine, Division of Pulmonary and Critical Care, Allergy and Clinical Immunology and the Konishi-MUSC Institute for Inflammation Research, Medical University of South Carolina, Charleston 29425, USA. kaplana@musc.edu
Joseph
K
K
Shibayama
Y
Y
Reddigari
S
S
Ghebrehiwet
B
B
D002352:Carrier Proteins; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D005174:Factor XII / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors; D007633:Keratins / Q000378:metabolism; D019679:Kininogen, High-Molecular-Weight / Q000378:metabolism*; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins; D011288:Prekallikrein / Q000378:metabolism; D011951:Receptors, Complement / Q000378:metabolism
C087299:C1QBP protein, human; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D019679:Kininogen, High-Molecular-Weight; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; C032402:complement 1q receptor; D007633:Keratins; D005174:Factor XII; D011288:Prekallikrein