Effect of cleavage of the heavy chain of human plasma kallikrein on its functional properties

Détails

ID Serval
serval:BIB_3509E69DE838
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Effect of cleavage of the heavy chain of human plasma kallikrein on its functional properties
Périodique
Blood
Auteur(s)
Colman  R. W., Wachtfogel  Y. T., Kucich  U., Weinbaum  G., Hahn  S., Pixley  R. A., Scott  C. F., de Agostini  A., Burger  D., Schapira  M.
ISSN
0006-4971 (Print)
Statut éditorial
Publié
Date de publication
02/1985
Volume
65
Numéro
2
Pages
311-8
Notes
Comparative Study
In Vitro
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Feb
Résumé
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.
Mots-clé
Blood Coagulation Tests Cell Aggregation/drug effects Complement C1 Inactivator Proteins/pharmacology Enzyme Activation Factor XII/biosynthesis Factor XIIa Humans Kallikreins/antagonists & inhibitors/biosynthesis/*blood/pharmacology Molecular Weight Neutrophils/metabolism/physiology Pancreatic Elastase/blood Peptide Fragments/biosynthesis
Pubmed
Web of science
Création de la notice
25/01/2008 15:27
Dernière modification de la notice
20/08/2019 13:22
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