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Abstract
Convulxin (CVX), a C-type lectin-like protein isolated from the venom of the snake species, Crotalus durissus terrificus, stimulates platelet aggregation by acting as a collagen receptor agonist for glycoprotein VI found in the platelets. The effect of CVX on platelets has been studied, but its effect on human peripheral blood mononuclear cells (PBMCs) remains unclear. Given the significance of PBMCs in inflammation, this study explored the effect of CVX on PBMCs, specifically regarding NLRP3 inflammasome activation by assessing cell viability, ability to induce cell proliferation, reactive oxygen species (ROS) and nitric oxide production, interleukin (IL)-2 and IL-10 secretion, NLRP3 complex activation, and the role of C-type lectin-like receptors (CTLRs) in these. CVX was not toxic to PBMCs at the investigated concentrations and did not increase PBMC growth or IL-2 release; however, CVX induced IL-10 release and ROS generation via monocyte activation. It also activated the NLRP3 complex, resulting in IL-1β induction. Furthermore, the interaction between CVX and Dectin-2, a CTLR, induced IL-10 production. CVX interaction with CTLR has been demonstrated by laminarin therapy. Because of the involvement of residues near the Dectin-2 carbohydrate-recognition site, the generation of ROS resulted in inflammasome activation and IL-1β secretion. Overall, this work helps elucidate the function of CVX in immune system cells.
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1 Oswaldo Cruz Foundation, FIOCRUZ Rondônia, Laboratory of Cellular Immunology Applied to Health, Porto Velho, Brazil (GRID:grid.418068.3) (ISNI:0000 0001 0723 0931)
2 São Paulo State University, UNESP, Department of Physics and Biophysics, Institute of Biosciences, Botucatu, Brazil (GRID:grid.410543.7) (ISNI:0000 0001 2188 478X)
3 Federal University of Amapá, Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Macapá, Brazil (GRID:grid.440559.9) (ISNI:0000 0004 0643 9014)
4 Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Center of Biomolecules Applied to Health (CEBio), Porto Velho, Brazil (GRID:grid.418068.3) (ISNI:0000 0001 0723 0931)
5 Oswaldo Cruz Foundation, FIOCRUZ Rondônia, Laboratory of Cellular Immunology Applied to Health, Porto Velho, Brazil (GRID:grid.418068.3) (ISNI:0000 0001 0723 0931); Federal University of Rondônia, UNIR, Department of Medicine, Porto Velho, Brazil (GRID:grid.440563.0) (ISNI:0000 0000 8804 8359)