Inflammation and coagulation crosstalk induced by BJcuL, a galactose-binding lectin isolated from Bothrops jararacussu snake venom

Author(s)

Cezarette, G. N. ; Sartim, M. A. ; Sampaio, S. V.

• Document type: Journal article
• Source: International Journal of Biological Macromolecules; v. 144, p. 9-pg., 2020-02-01.

Abstract

Inflammation and coagulopathies are important systemic events following snakebite. Snake venom galactoside-binding lectins (SVgalLs) are known modulators of the immune response with no direct effect on hemostasis. Considering the crosstalk between inflammation and coagulation, the present study investigated how BJcuL, a proinflammatory SVgalL isolated from Bothrops jararacussu venom, mediated the inflammation-induced procoagulant activity. We examined the proinflammatory cytokine production and procoagulant tissue factor (TF) activity in human whole blood and monocyte-rich cell suspension (MR-PBMC) treated with BJcuL. This lectin increased production of the cytokines TNF-alpha, IL-1 beta and IL-6, upregulated TF expression on the cell surface, and induced procoagulant activity. The proinflammatory behavior was mediated by the direct interaction between the lectin and toll-like receptor 4, via binding to beta-galactoside-containing glycoconjugates on the cell surface, and activation of NF kappa-B signaling. Interestingly, the BJcuL-induced inflammation was directly associated with the procoagulant activity of MR-PBMC cells. In whole blood culture, the lectin exhibited similar behavior, i.e. it induced cytokine production and MR-PBMC TF-mediated procoagulant activity. Therefore, the present study is the first report on the inflammation-induced procoagulant activity of SVgalLs, and it indicates that BJcuL is an important factor associated with coagulopathy in patients with snake envenomation. (C) 2019 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis
• Grantee: Suely Vilela
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/06290-6 - Evaluation of anti-inflammatory potential of crotoxin, a phospholipase A2 isolated from Crotalus durissus terrificus venom, in a disseminated intravascular coagulation model induced by endotoxemia
• Grantee: Marco Aurélio Sartim
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/04079-9 - Anti-inflammatory potential evaluation of crotoxin, a phospholipase A2 isolated from the venom of Crotalus durissus terrificus, in endotoxemia model
• Grantee: Gabriel Neves Cezarette
• Support Opportunities: Scholarships in Brazil - Scientific Initiation