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

Autor: Zychar BC; Laboratory of Pathophysiology, Butantan Institute, São Paulo, 05503-900, Brazil., Clissa PB; Laboratory of Immunopathology, Butantan Institute, São Paulo, 05503-900, Brazil., Carvalho E; Laboratory of Bacteriology, Butantan Institute, São Paulo, 05503-900, Brazil., Baldo C; Department of Biochemistry and Biotechnology, State University of Londrina, Paraná, 86057-970, Brazil., Gonçalves LRC; Laboratory of Pathophysiology, Butantan Institute, São Paulo, 05503-900, Brazil. Electronic address: luis.goncalves@butantan.gov.br.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2020 Jan 08; Vol. 521 (2), pp. 402-407. Date of Electronic Publication: 2019 Oct 25.
DOI: 10.1016/j.bbrc.2019.10.144
Abstrakt: 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.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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