A radioimmunoassay for the detection of molecular forms of human plasma kininogen

Abstract

Kininogen is a heterogenous plasma glycoprotein and source of the vasoactive kinin peptides. Two main forms of human kininogen are well known, the high molecular mass (Wr 120 000) and the low molecular mass (IiWr 50 000-78 000) kininogens [l-3]. I-I$ kininogen functions as a cofactor in the contact activation of F XIIa and F XIa [4]. The cascade reactions leading to the formation of fibrin in the intrinsic pathway of blood coagulation also involve activation of kallikrein (EC 3.4.2 1.8) in an amplifying feedback mechanism between prekallikrein and F XII. A small amount of surface-bound F XII has been shown to catalyze the formation of low levels of kallikrein. Whether these reactions shown to occur in vitro when blood plasma comes into contact with glass occur under physiological conditions is not yet known [5,6]. The two molecular forms differ primarily by the structure of their respective light chain, which in the HMr kininogen contains a histidine-rich fragment responsible for the coagulation effect and covalently bound to the heavy chain through the vasoactive peptide segment (bradykinin). However, UM, is present in normal human plasma in a higher concentration while HMr kininogen constitutes an average 15% of the total kininogen content [7,8]. A relationship between the two molecular forms has been suggested