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

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: Biochemical and Biophysical Research Communications; v. 521, n. 2, p. 402-407, JAN 8 2020.
• Web of Science Citations: 0

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 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)

• FAPESP's process: 08/00108-8 - Role of different domains of Bothrops metaloproteases on the expression of adhesion alteractions leukocyte-endothelium interaction of the microcirculation of murine cremaster: action of proteases inhibitors
• Grantee: Bianca Cestari Zychar
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/09002-8 - Structural and functional characterization of a protein isolated from Bothrops jararaca snake plasma, related to the mammalian high molecular weight kininogen
• Grantee: Luis Roberto de Camargo Gonçalves
• Support Opportunities: Regular Research Grants