Abstract
BackgroundTityus serrulatus scorpion venom (TsV) contains toxins that act on K+ and Na+ channels and account for the venom’s toxic effects. TsV can activate murine peritoneal macrophages, but its effects on human lymphocytes have been poorly investigated. Considering that lymphocytes may play an important role in envenomation, we assessed whether TsV affects the expression of phenotypic (CD3, CD4, and CD8) and activation (CD69, CD25, and HLA-DR) markers, cell proliferation, and cytokine production in peripheral blood mononuclear cells.MethodsCytotoxicity of TsV was evaluated via the MTT assay. Cell proliferation, expression of phenotypic and activation markers, and release of cytokines were assessed using flow cytometry, after treatment with non-cytotoxic concentrations of TsV. The combined use of carboxyfluorescein diacetate succinimidyl ester and monoclonal antibodies against phenotypic and activation markers enabled us to simultaneously assess cell proliferation extent and cell activation status, and to discriminate among cell subpopulations.ResultsTsV at concentrations of 25 to 100 μg/mL were not cytotoxic towards peripheral blood mononuclear cells. TsV did not induce significant changes in lymphocyte subpopulations or in the expression of activation markers on CD4+ and CD8+ T cells. TsV inhibited the phytohemagglutinin-stimulated lymphocyte proliferation, particularly in the CD8+ CD25+ T lymphocyte subset. TsV alone, at 50 and 100 μg/mL, did not induce peripheral blood mononuclear cell proliferation, but elicited the production and release of IL-6, a proinflammatory cytokine that plays an important role in innate and adaptive immune responses.ConclusionsTsV is a potential source of molecules with immunomodulatory action on human T lymphocytes.Electronic supplementary materialThe online version of this article (doi:10.1186/s40409-015-0046-3) contains supplementary material, which is available to authorized users.
Highlights
Tityus serrulatus scorpion venom (TsV) contains toxins that act on K+ and Na+ channels and account for the venom’s toxic effects
Considering that TsV contains several toxins that act on membrane K+ channels, and that these channels are involved in the regulation of cellular functions, in the present study we examined whether TsV interferes in peripheral blood mononuclear cell (PBMC) cytokine production, as well as in T lymphocyte phenotype, proliferation, and expression of activation markers
TsV inhibits the proliferation of CD8+CD25+ T lymphocytes In PBMC previously stimulated with PHA, the 96-h treatment with TsV at 25, 50 or 100 μg/mL reduced the Cytokine quantification The levels of tumor necrosis factor-α (TNF-α), IL-2, IL-4, IL-6, IL-10, IL-17, and IFN-γ in culture supernatants of PBMC (1.0 × 105 cells) treated with PHA (2 μg/mL) and/ or TsV (25, 50, and 100 μg/mL) for 96 h were quantified by flow cytometry, using the assay kit Cytometric Bead Array (CBA) Human Th1/Th2/Th17 Cytokine (BD Biosciences, USA) according to the manufacturer’s instructions
Summary
Tityus serrulatus scorpion venom (TsV) contains toxins that act on K+ and Na+ channels and account for the venom’s toxic effects. Tityus is one genus of this family, of which Tityus serrulatus is the most dangerous species – Scorpion venom is composed of numerous toxins, mostly of peptides and neurotoxins, which act by deregulating cell membrane ion channels. Such toxins may cause pain, deregulation of cardiovascular and autonomic nervous systems, vomiting, abdominal pain, stimulation of peripheral nervous system, neuromuscular excitation, among other deleterious effects in humans [8]. The participation of proinflammatory cytokines in the moderate and severe envenomation pathophysiology indicates that these patients may benefit from treatment with glucocorticoids
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