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REVIEW: Contact System. New Concepts on Activation Mechanisms and Bioregulatory Functions

G. A. Yarovaya*, T. B. Blokhina, and E. A. Neshkova

Department of Biochemistry, Russian Medical Academy of Postgraduate Education, Barrikadnaya ul. 2/1, Moscow, 123995 Russia; fax: (095) 945-2415; E-mail: acadbio@orc.ru; yarov@aha.ru

* To whom correspondence should be addressed.

Received July 3, 2001; Revision received September 18, 2001
This review considers the data of recent years concerning the contact system initiating the activation of blood plasma proteolytic systems, such as hemocoagulation, fibrinolysis, kininogenesis, and also complement and angiotensinogenesis. The main proteins of the contact system are the factors XII and XI, prekallikrein, and high-molecular-weight kininogen. The data on the structure, functions, and biosynthesis of these proteins and on their genes are presented. Studies in detail on the protein-protein interactions during formation of the ensemble of the contact system components on the anionic surface resulted in the postulation of the mechanism of activation of this system associated with generation of the XIIa factor and of kallikrein. This mechanism is traditionally considered a trigger of processes for the internal pathway of the hemocoagulating cascade. However, the absence of direct confirmation of such activation in vivo and the absence of hemorrhagia in the deficiency of these components stimulated the studies designed to find another mechanism of their activation and physiological role outside of the hemostasis system. As a result, a new concept on the contact system activation on the endothelial cell membrane was proposed. This concept is based on the isolation of a complex of proteins, which in addition to the above-mentioned proteins includes cytokeratin 1 and the receptors of the urokinase-like plasminogen activator and of the complement q-component. The ideas on the role of this system in the biology of vessels are developed. Some of our findings on the effect of leukocytic elastase on the key components of the contact system are also presented.
KEY WORDS: contact system, factor XII, factor XI, prekallikrein, kallikrein, high-molecular-weight kininogen, polyanionic surface, endothelial cells, ensemble of the contact system components, activity regulation