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.