Laboratory of Cellular Immunology Applied to Health, Oswaldo Cruz Foundation, FIOCRUZ Rondônia, Porto Velho, RO, Brazil.
Department of Physics and Biophysics, Institute of Biosciences, São Paulo State University, UNESP, Botucatu, SP, Brazil.
Sci Rep. 2022 Mar 18;12(1):4706. doi: 10.1038/s41598-022-08735-7.
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.
凝聚素(CVX)是从蛇种 Crotalus durissus terrificus 的毒液中分离出来的 C 型凝集素样蛋白,通过作为血小板中糖蛋白 VI 的胶原受体激动剂刺激血小板聚集。已经研究了 CVX 对血小板的作用,但它对人外周血单核细胞(PBMC)的作用尚不清楚。鉴于 PBMC 在炎症中的重要性,本研究探讨了 CVX 对 PBMC 的影响,特别是通过评估细胞活力、诱导细胞增殖、活性氧(ROS)和一氧化氮产生、白细胞介素(IL)-2 和 IL-10 分泌、NLRP3 复合物激活以及 C 型凝集素样受体(CTLRs)在这些中的作用来研究 NLRP3 炎性小体的激活。在所研究的浓度下,CVX 对 PBMC 没有毒性,也不会增加 PBMC 生长或 IL-2 释放;然而,CVX 通过单核细胞激活诱导 IL-10 释放和 ROS 生成。它还激活了 NLRP3 复合物,导致 IL-1β的诱导。此外,CVX 与 CTLR Dectin-2 的相互作用诱导了 IL-10 的产生。通过薄层层析疗法已经证明了 CVX 与 CTLR 的相互作用。由于涉及到 Dectin-2 碳水化合物识别位点附近的残基,ROS 的产生导致了炎性小体的激活和 IL-1β的分泌。总的来说,这项工作有助于阐明 CVX 在免疫系统细胞中的功能。