Leukocyte recruitment induced by snake venom metalloproteinases: Role of the catalytic domain

Autor(es)

Zychar, Bianca Cestari ^[1] ; Clissa, Patricia Bianca ^[2] ; Carvalho, Eneas ^[3] ; Baldo, Cristiani ^[4] ; Goncalves, Luis Roberto C. ^[1]

Afiliação do(s) autor(es)

^[1] Butantan Inst, Lab Pathophysiol, Av Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil

^[2] Butantan Inst, Lab Immunopathol, BR-05503900 Sao Paulo - Brazil

^[3] Butantan Inst, Lab Bacteriol, BR-05503900 Sao Paulo - Brazil

^[4] Univ Estadual Londrina, Dept Biochem & Biotechnol, BR-86057970 Londrina, Parana - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Biochemical and Biophysical Research Communications; v. 521, n. 2, p. 402-407, JAN 8 2020.
• Citações Web of Science: 0

Resumo

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 BnPI 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. (C) 2019 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 08/00108-8 - Papel do diferentes domínios de metaloproteases de venenos botrópicos nas alterações da interação leucócito-endotélio da microcirculação do músculo cremaster de camundongos: ação de inibidores de proteases
• Beneficiário: Bianca Cestari Zychar
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/09002-8 - Caracterização estrutural e funcional de uma proteína isolada do plasma de serpentes Bothrops jararaca, relacionada ao cininogênio de alto peso molecular de mamíferos
• Beneficiário: Luis Roberto de Camargo Gonçalves
• Modalidade de apoio: Auxílio à Pesquisa - Regular