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Effect of cleavage of the heavy chain of human plasma kallikrein on its
functional properties
RW Colman, YT Wachtfogel, U Kucich, G Weinbaum, S Hahn, RA Pixley, CF Scott, A de Agostini, D Burger and M Schapira
Human plasma kallikrein consists of an N-terminal heavy chain of molecular
weight (mol wt) 52,000, linked by disulfide bonds to two light chain
variants (mol wt 36,000 or 33,000). Although the active catalytic site of
kallikrein resides on the C-terminal light chain, the role of the
N-terminal heavy chain is less clear. We therefore studied an enzyme
designated beta-kallikrein, containing a single cleavage in the heavy chain
(mol wt 28,000 + 18,000) and compared it to the enzyme, alpha-kallikrein,
with an intact heavy chain. The rates of inactivation by C1 inhibitor of
plasma alpha- and beta-kallikreins were kinetically identical, as measured
by residual amidolytic activity, after various times of incubation with the
inhibitor. Both enzymes reacted completely with C1 inhibitor after 18 hours
and formed identical C1 inhibitor- kallikrein complexes of mol wt 195,000.
The rate of activation of factor XII by alpha-kallikrein and
beta-kallikrein was similar. In contrast, the rate of cleavage of high
molecular weight kininogen (HMWK) by alpha-kallikrein was at least fivefold
faster and the ratio of coagulant activity to amidolytic activity was
fourfold greater than for beta-kallikrein. Plasma alpha-kallikrein, at
concentrations potentially achievable in plasma, induced aggregation of
neutrophils, but beta-kallikrein failed to elicit this response. In
addition, human neutrophils pretreated with cytochalasin B released 2.46
+/- 0.10 microgram/10(7) cells of elastase antigen, but beta-kallikrein
released only 0.25 +/- 0.10 micrograms/10(7) cells. These observations
suggest that cleavage of the heavy chain influences the rate of cleavage of
HMWK and decreases its coagulant activity. Moreover, an intact heavy chain
appears to be requisite to support the ability of kallikrein to aggregate
neutrophils and release elastase.
Volume 65,
Issue 2,
pp. 311-318,
02/01/1985
Copyright © 1985 by The American Society of Hematology
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