INTERACTIONS OF PLASMA KALLIKREIN AND C1SBAR WITH NORMAL AND DYSFUNCTIONAL C1BAR-INHIBITOR PROTEINS FROM PATIENTS WITH HEREDITARY ANGIONEUROTIC-EDEMA - ANALYTIC GEL STUDIES

Abstract

Purified preparations of normal C.hivin.1-inhibitor (C.hivin.1-INH) formed high mol wt complexes with plasma kallikrein that were stable during sodium dodecyl sulfate (SDS)-gel electrophoresis, but most of the dysfunctional C.hivin.1-INH proteins isolated from plasma of patients with type II hereditary angioneurotic edema (HANE) did not. Two of eight dysfuctional C.hivin.1-INH proteins were cleaved to lower mol wt forms that were not seen following the reaction of normal C.hivin.1-INH with equimolar amounts, or less, of plasma kallikrein. Only the higher mol wt component of normal C.hivin.1-INH (106,000 mol wt) appeared to form a stable complex with the plasma kallikrein, whereas both the 106,000 and 96,000 mol wt forms made stable complexes with C1.hivin.s. When a preparation of normal C.hivin.1-INH containing a homogeneous single band of C.hivin.1-INH containing a homogeneous single band of C.hivin.1-INH was exposed to C1.hivin.s or kallikrein, a "doublet" form evolved in which the heaviest band was in the original position of native C.hivin.1-INH; C1.hivin.s cleavage provided a second band of 96,000; and cleavage by kallikrein, a second band of 94,000 mol wt. We conclude that dysfunctional C.hivin.1-INH proteins from plasma of persons with type II hereditary angioneurotic edema have impaired interactions with plasma kallikrein and are heterogeneous with respect to the interactions. Moreover, the requirements for the formation of stable complexes between normal C.hivin.1-INH and plasma kallikrein differed from those for stable complex formation with C1.hivin.s. The doublet form of C.hivin.1-INH, which purified preparations frequently demonstrate, may be due to prior cleavage by C1.hivin.s or kallikrein.