Department of BioMolecular Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil; School of Medicine, Centro Universitário Barão de Mauá (CBM), Ribeirão Preto, SP, Brazil.
Graduate Program in Genetics, Conservation and Evolutionary Biology (PPG GCBEv), National Institute for Amazon Research (INPA), Manaus, AM, Brazil.
Toxicon. 2023 Jul;230:107171. doi: 10.1016/j.toxicon.2023.107171. Epub 2023 May 19.
There are several scorpion species of medical relevance around the world. Some of them are well characterized by their toxins and clinical outcomes. Brazilian Amazon has a great amount of these arthropods that have an impact in the scorpionism events specifically in this region of Brazil. Recently, several studies pointed out the immune system activation during scorpion envenouming as an important facet of scorpionism, inducing a sepsis-like state that culminates in clinical severity and death. In this work, we characterized the macrophage response of three species of clinical relevance in Brazilian Amazon: Tityus silvestris, T. metuendus and T. obscurus and one specie with no toxic effects to humans, Brotheas amazonicus. All the four species analyzed were able to induce pro- and anti-inflammatory cytokine production in a J774.1 murine macrophage model. This activation was dependent on TLR2/TLR4/MyD88 activation and abolished by TLRs antagonists. These results suggest that the venoms of the four species analyzed were able to induce macrophage response in agreement to the well-established immune activation by T. serrulatus venom. Our findings provide new insights into the clinical repercussions of scorpionism of uncharacterized species and point to new biotechnological applications of these venoms and possible supportive therapies in scorpionism.
全世界有几种具有医学相关性的蝎子。其中一些因毒素和临床结果而被很好地描述。巴西亚马逊地区有大量的这些节肢动物,它们对该地区的蝎子蜇伤事件有影响。最近,一些研究指出,免疫系统在蝎子蜇伤时的激活是蝎子蜇伤的一个重要方面,它会导致类似败血症的状态,最终导致临床严重程度和死亡。在这项工作中,我们对巴西亚马逊地区三种具有临床相关性的蝎子(Tityus silvestris、T. metuendus 和 T. obscurus)和一种对人类没有毒性的蝎子(Brotheas amazonicus)进行了巨噬细胞反应特征分析。所有四种分析的物种都能够在 J774.1 鼠巨噬细胞模型中诱导促炎和抗炎细胞因子的产生。这种激活依赖于 TLR2/TLR4/MyD88 的激活,并被 TLR 拮抗剂所阻断。这些结果表明,四种分析的毒液都能够诱导巨噬细胞反应,这与 T. serrulatus 毒液所建立的免疫激活相一致。我们的研究结果为未明确特征的蝎子蜇伤的临床影响提供了新的见解,并为这些毒液的新生物技术应用和蝎子蜇伤的可能支持性治疗指明了方向。