首页 | 本学科首页   官方微博 | 高级检索  
     


Leukocyte recruitment induced by snake venom metalloproteinases: Role of the catalytic domain
Affiliation:1. Laboratory of Pathophysiology, Butantan Institute, São Paulo, 05503-900, Brazil;2. Laboratory of Immunopathology, Butantan Institute, São Paulo, 05503-900, Brazil;3. Laboratory of Bacteriology, Butantan Institute, São Paulo, 05503-900, Brazil;4. Department of Biochemistry and Biotechnology, State University of Londrina, Paraná, 86057-970, Brazil;1. Research and Development Center, Ezequiel Dias Foundation, Belo Horizonte, MG, Brazil;2. Center for Data and Knowledge Integration for Health, Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, BA, Brazil;3. Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany;1. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (FCFRP-USP), Ribeirão Preto, SP, Brazil;2. Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia (ICBIM-UFU), Uberlândia, MG, Brazil;3. Instituto Nacional de Ciência e Tecnologia em Nano-Biofarmacêutica (N-Biofar), Belo Horizonte, MG, Brazil;1. Departamento de Biofísica e Farmacologia, Instituto de Biociências, UNESP – Universidade Estadual Paulista, Botucatu, SP, Brazil;2. Graduate Program in Tropical Diseases, Faculdade de Medicina de Botucatu (FMB) and Centro de Estudos de Venenos e Animais Peçonhentos (CEVAP), UNESP – Universidade Estadual Paulista, Botucatu, SP, Brazil;1. Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;2. Biochemistry Research Division, Department of Medical Research, Yangon, Myanmar;3. Genome Technology Research Unit, National Center for Genetic Engineering and Biotechnology, PathumThani, Thailand;4. Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom;5. Ingenet Limited, London, United Kingdom;1. Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, 11501, Costa Rica;2. European Molecular Biology Laboratory, Heidelberg, 69117, Germany
Abstract:Snake venom metalloproteinases (SVMPs) are key toxins involved in local inflammatory reactions after snakebites. This study aimed to investigate the effect of SVMP domains on the alterations in leukocyte-endothelium interactions in the microcirculation of mouse cremaster muscle. We studied three toxins: BnP1, a PI-toxin isolated from Bothrops neuwiedi venom, which only bears a catalytic domain; Jararhagin (Jar), a PIII-toxin isolated from Bothrops jararaca venom with a catalytic domain, as well as ECD-disintegrin and cysteine-rich domains; and Jar-C, which is produced from the autolysis of Jar and devoid of a catalytic domain. All these toxins induced an increase in the adhesion and migration of leukocytes. By inhibiting the catalytic activity of Jar and BnP1 with 1.10-phenanthroline (oPhe), leukocytes were no longer recruited. Circular dichroism analysis showed structural changes in oPhe-treated Jar, but these changes were not enough to prevent the binding of Jar to collagen, which occurred through the ECD-disintegrin domain. The results showed that the catalytic domain of SVMPs is the principal domain responsible for the induction of leukocyte recruitment and suggest that the other domains could also present inflammatory potential only when devoid of the catalytic domain, as with Jar-C.
Keywords:Snake venom metalloproteinases  Leukocyte recruitment  Zinc-binding domain  Microcirculation
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号