Modulation of Adhesion Molecules Expression by Different Metalloproteases Isolated from Bothrops Snakes.

Bianca C Zychar,Eneas Carvalho,Patrícia B Clissa,Adilson S Alves,Cristiani Baldo,Eliana L Faquim-Mauro,Luís Roberto C Gonçalves

doi:10.3390/toxins13110803

Bianca C Zychar, Eneas Carvalho + Show 5 more

Open Access

https://doi.org/10.3390/toxins13110803

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Abstract

Snake venom metalloproteinases (SVMP) are involved in local inflammatory reactions observed after snakebites. Based on domain composition, they are classified as PI (pro-domain + proteolytic domain), PII (PI + disintegrin-like domains), or PIII (PII + cysteine-rich domains). Here, we studied the role of different SVMPs domains in inducing the expression of adhesion molecules at the microcirculation of the cremaster muscle of mice. We used Jararhagin (Jar)—a PIII SVMP with intense hemorrhagic activity, and Jar-C—a Jar devoid of the catalytic domain, with no hemorrhagic activity, both isolated from B. jararaca venom and BnP-1—a weakly hemorrhagic P1 SVMP from B. neuwiedi venom. Toxins (0.5 µg) or PBS (100 µL) were injected into the scrotum of mice, and 2, 4, or 24 h later, the protein and gene expression of CD54 and CD31 in the endothelium, and integrins (CD11a and CD11b), expressed in leukocytes were evaluated. Toxins induced significant increases in CD54, CD11a, and CD11b at the initial time and a time-related increase in CD31 expression. In conclusion, our results suggest that, despite differences in hemorrhagic activities and domain composition of the SVMPs used in this study, they behave similarly to the induction of expression of adhesion molecules that promote leukocyte recruitment.

Highlights

Snakebite accidents in humans are a severe global health problem that mainly affects the poor and economically active population, causing significant social issues [1,2]
This study investigated the effects of different Snake venom metalloproteinases (SVMP) domains on modulating the expression of adhesion molecules on leukocytes and the microvasculature of mice exposed to three different toxins isolated from Bothrops venoms: Jar and Jar-C, which are a PIII-SVMP and disintegrin-like protein isolated from Bothrops jararaca venom (BjV), respectively, and BnP1, a PI-SVMP with weak hemorrhagic action isolated from Bothrops neuwiedi venoms (BnV)
The microcirculation of the cremaster muscle in animals injected with the toxins Jar, Jar-C, and BnP1 presented positive labeling for both adhesion molecules compared to the microcirculation of the control group

Summary

Introduction

Snakebite accidents in humans are a severe global health problem that mainly affects the poor and economically active population, causing significant social issues [1,2]. The World Health Organization (WHO) estimates that approximately 2.7 million snakebite accidents occur annually worldwide. In Brazil, an average of 29,000 snakebites occur annually, resulting in approximately 120 deaths/year [5], in addition to underreported cases. Of these 29,000 envenomations, approximately 90% are caused by snakes of the Bothrops genus [6]. In Bothrops snakebites, severe tissue loss at the site of the bite is observed as a result of hemorrhage and an exacerbated local inflammatory response induced by the venom

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