Interactions of plasma kallikrein and C1-s with normal and dysfunctional
C1(-)-inhibitor proteins from patients with hereditary angioneurotic edema:
analytic gel studies
VH Donaldson, CJ Wagner, B Tsuei, G Kindness, DH Bing, RA Harrison and FS Rosen
Purified preparations of normal C1(-)-inhibitor (C1(-)-INH) formed high mol
wt complexes with plasma kallikrein that were stable during sodium dodecyl
sulfate (SDS)-gel electrophoresis, but most of the dysfunctional C1(-)-INH
proteins isolated from plasma of patients with type II hereditary
angioneurotic edema (HANE) did not. Two of eight dysfunctional C1(-)-INH
proteins were cleaved to lower mol wt forms that were not seen following
the reaction of normal C1(-)-INH with equimolar amounts, or less, of plasma
kallikrein. Only the higher mol wt component of normal C1(-)-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-s. When a preparation of normal C1(-)-INH containing a homogeneous
single band of C1(-)-INH was exposed to C1-s or kallikrein, a "doublet"
form evolved in which the heaviest band was in the original position of
native C1(-)-INH; C1- 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 C1(-)-INH proteins from plasma of persons with type II
hereditary angioneurotic edema have impaired interactions with plasma
kallikrein and are heterogeneous with respect to these interactions.
Moreover, the requirements for the formation of stable complexes between
normal C1(-)-INH and plasma kallikrein differed from those for stable
complex formation with C1-s. The doublet form of C1(-)-INH, which purified
preparations frequently demonstrate, may be due to prior cleavage by C1-s
or kallikrein.
Volume 69,
Issue 4,
pp. 1096-1101,
04/01/1987
Copyright © 1987 by The American Society of Hematology
