Gremski Luiza Helena, Trevisan-Silva Dilza, Ferrer Valéria Pereira, Matsubara Fernando Hitomi, Meissner Gabriel Otto, Wille Ana Carolina Martins, Vuitika Larissa, Dias-Lopes Camila, Ullah Anwar, de Moraes Fábio Rogério, Chávez-Olórtegui Carlos, Barbaro Katia Cristina, Murakami Mario Tyago, Arni Raghuvir Krishnaswamy, Senff-Ribeiro Andrea, Chaim Olga Meiri, Veiga Silvio Sanches
Departamento de Biologia Celular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil; Departamento de Patologia Clínica, Hospital de Clínicas, Universidade Federal do Paraná, Brazil.
Departamento de Biologia Celular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
Toxicon. 2014 Jun;83:91-120. doi: 10.1016/j.toxicon.2014.02.023. Epub 2014 Mar 11.
The Loxosceles genus spiders (the brown spiders) are encountered in all the continents, and the clinical manifestations following spider bites include skin necrosis with gravitational lesion spreading and occasional systemic manifestations, such as intravascular hemolysis, thrombocytopenia and acute renal failure. Brown spider venoms are complex mixtures of toxins especially enriched in three molecular families: the phospholipases D, astacin-like metalloproteases and Inhibitor Cystine Knot (ICK) peptides. Other toxins with low level of expression also present in the venom include the serine proteases, serine protease inhibitors, hyaluronidases, allergen factors and translationally controlled tumor protein (TCTP). The mechanisms by which the Loxosceles venoms act and exert their noxious effects are not fully understood. Except for the brown spider venom phospholipase D, which causes dermonecrosis, hemolysis, thrombocytopenia and renal failure, the pathological activities of the other venom toxins remain unclear. The objective of the present review is to provide insights into the brown spider venoms and loxoscelism based on recent results. These insights include the biology of brown spiders, the clinical features of loxoscelism and the diagnosis and therapy of brown spider bites. Regarding the brown spider venom, this review includes a description of the novel toxins revealed by molecular biology and proteomics techniques, the data regarding three-dimensional toxin structures, and the mechanism of action of these molecules. Finally, the biotechnological applications of the venom components, especially for those toxins reported as recombinant molecules, and the challenges for future study are discussed.
巴西游走蛛属蜘蛛（棕色蜘蛛）在各大洲均有发现，蜘蛛叮咬后的临床表现包括皮肤坏死且坏死区域因重力作用扩散，偶尔还会出现全身症状，如血管内溶血、血小板减少和急性肾衰竭。棕色蜘蛛毒液是复杂的毒素混合物，尤其富含三个分子家族的毒素：磷脂酶D、类虾红素金属蛋白酶和抑制性胱氨酸结（ICK）肽。毒液中还存在其他低表达水平的毒素，包括丝氨酸蛋白酶、丝氨酸蛋白酶抑制剂、透明质酸酶、变应原因子和翻译控制肿瘤蛋白（TCTP）。巴西游走蛛毒液发挥作用并产生有害影响的机制尚未完全明确。除了导致皮肤坏死、溶血、血小板减少和肾衰竭的棕色蜘蛛毒液磷脂酶D外，其他毒液毒素的病理活性仍不清楚。本综述的目的是基于近期研究结果，深入探讨棕色蜘蛛毒液和巴西游走蛛咬伤中毒。这些见解包括棕色蜘蛛的生物学特性、巴西游走蛛咬伤中毒的临床特征以及棕色蜘蛛叮咬的诊断和治疗。关于棕色蜘蛛毒液，本综述包括分子生物学和蛋白质组学技术揭示的新型毒素的描述、三维毒素结构的数据以及这些分子的作用机制。最后，讨论了毒液成分的生物技术应用，特别是那些报道为重组分子的毒素，以及未来研究面临的挑战。
