Journal Article

Extended cleavage specificity of the mast cell chymase from the crab-eating macaque (<i>Macaca fascicularis</i>): an interesting animal model for the analysis of the function of the human mast cell chymase

Michael Thorpe, Jing Yu, Vamsi Boinapally, Parvin Ahooghalandari, Jukka Kervinen, Lawrence de Garavilla and Lars Hellman

in International Immunology Meeting Abstracts

Published on behalf of Japanese Society for Immunology

Volume 24, issue 12, pages 771-782
Published in print December 2012 |
Published online September 2012 | | DOI: http://dx.doi.org/10.1093/intimm/dxs081

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Serine proteases are the major protein constituents within mast cell secretory granules. These proteases are subdivided into chymases and tryptases depending on their primary cleavage specificity. Here, we present the extended cleavage specificity of the macaque mast cell chymase and compare the specificity with human chymase (HC) and dog chymase (DC) that were produced in the same insect cell expression host. The macaque chymase (MC) shows almost identical characteristics as the HC, including both primary and extended cleavage specificities as well as sensitivity to protease inhibitors, whereas the DC differs in several of these characteristics. Although previous studies have shown that mouse mast cell protease-4 (mMCP-4) is similar in its hydrolytic specificity to the HC, mouse mast cells contain several related enzymes. Thus mice may not be the most appropriate model organism for studying HC activity and inhibition. Importantly, macaques express only one chymase and, as primates, are closely related to human general physiology. In addition, the human and macaque enzymes both cleave angiotensin I (Ang I) in the same way, generating primarily angiotensin II (Ang II) and they do not further degrade the peptide like most rodent enzymes do. Both enzymes also cleave two additional potential in vivo substrates, fibronectin and secretory leukocyte protease inhibitor (SLPI) in a similar way. Given the fact that both HC and MC are encoded by a single gene with high sequence homology and that many physiological processes are similar between these species, the macaque may be a very interesting model to study the physiological role of the chymase and to determine the potency and potential side-effects of various chymase inhibitors designed for therapeutic human use.

Keywords: animal model; chymase; cleavage specificity; human chymase; mast cell; macaque

Journal Article.  7718 words.  Illustrated.

Subjects: Immunology ; Biochemical Immunology

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