Jararaca GPIb-binding protein causes thrombocytopenia during Bothrops jararaca envenomation
Year: 2024
Type: article
Abstract: Inoculation of Bothrops jararaca snake venom (BjV) induces thrombocytopenia in humans and various animal species. Although several BjV toxins acting on hemostasis have been well characterized in vitro, it is not known which one is responsible for inducing thrombocytopenia in vivo. In previous studies, we showed that BjV incubated with metalloproteinase or serine proteinase inhibitors and/or anti-botrocetin antibodies still induced thrombocytopenia in rats and mice. Thus, herein we identified and characterized BjV toxins responsible for inducing thrombocytopenia. Initially, by filtering BjV on ultrafiltration systems, proteins with molecular masses between 30 and 50 kDa were shown to induce thrombocytopenia in mice, but they were not associated with hemorrhagic or coagulating activities. The 50 kDa ultrafiltrate was chromatographed, and two proteins (named fraction D and fraction E) induced thrombocytopenia in mice. However, neither fraction D nor fraction E induced platelet aggregation in platelet-rich plasma or whole blood from humans or mice. By mass spectrometry analysis, fraction E was identified as jararaca glycoprotein Ib (GPIb)-binding protein. Injection of these fractions caused thrombocytopenia in control or Vwf −/− mice, showing that the axis platelet GPIb – von Willebrand factor is not involved in their biological action in vivo. New studies are necessary to understand how these proteins act in vivo.
Source: Scientific Reports
Institutions: Universidade de São Paulo, Instituto Butantan, Universidade Federal de São Paulo, Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidade Federal da Integração Latino-Americana, Administración Nacional de Laboratorios e Institutos de Salud, Instituto Nacional de Medicina Tropical
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,590
Funders: Fundação de Amparo à Pesquisa do Estado de São Paulo, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Governo Brasil, Consejo Nacional de Investigaciones Científicas y Técnicas, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Butantan, Universidade Estadual de Campinas, Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación
Awards: G1020320157, G1107239341, G1116620415, CeTICS - Center of Toxins, Immune-Response and Cell Signaling, G133236826, G154860134, Inhibitor and proteases of ectoparasites: relationship of structure-function and identification of the role of these molecules in the interaction of diseases vector e their etiological agents, G2764560170, G295657101, G3184663708, Use of phage display as a tool in the diagnosis and control of diseases transmitted by hematophagous vectors, G4514990744, G4825398508, G5053655580, G5547626716, G607208967, Hemostasis-inflammation interaction during envenomation by Bothrops jararaca snakes: pathogenesis of thrombocytopenia, and therapeutic anti-ophidian mechanisms of quercetin-3-rutinoside (rutin), G7120492524, Involvement of Von Willebrand factor in hemostatic disturbances induced by Bothrops jararaca snake venom: experimental study, Isolation and characterization of Brothrops jararaca snake venom proteins that induce thrombocytopenia
OpenAlex ID: W4405896147