Significant Role of Fragment 1·2 Plus Light Chain of Bovine High Molecular Weight Kininogen in Contact Mediated Coagulation

Abstract

We have previously reported that high molecular weight kininogen (HMWK) partially corrects the partial thromboplastin time (aPTT) of Fitzgerald Trait plasma (HMWK deficiency), and in addition, we have also reported that kinin free HMWK which is also Fragment 1·2 free has decreased correcting capability. Presently, we have studied the effect of lysyl-bradykinin-free HMWK with Fragment 1·2 intact, obtained by hydrolysis of HMWK with urinary kallikrein. In addition, the effect of light chain with and without attached Fragment 1·2 were studied. When the correcting capacity of HMWK was compared, on a molar basis with the above-mentioned fragments, the following results were obtained. Kinin and Fragment 1.2 free HMWK has a significantly decreased correcting capacity on the aPTT of Fitzgerald trait plasma while lysyl-bradykinin free HMWK shows no decrease in correcting capability. Light chain with Fragment 1·2 attached also has intact correcting capability while light chain alone has a significantly decreased correcting activity. The above data suggest that the active site of HMWK resides in the light chain with Fragment 1·2 attached. Since Fragment 1·2 alone has inhibitory capacity, it may serve as a binding site and the light chain as the active site.