Jararaca GPIb-binding protein causes thrombocytopenia during Bothrops jararaca envenomation
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 previo...
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Nature Portfolio
2024-12-01
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| Online Access: | https://doi.org/10.1038/s41598-024-81851-8 |
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| author | Marcelo Larami Santoro Ana Teresa Azevedo Sachetto Jaqueline Gomes Rosa Ricardo José Soares Torquato Débora Andrade-Silva Dilza Trevisan-Silva Cynthia Zaccanini de Albuquerque Solange M. T. Serrano Vânia Gomes de Moura Mattaraia Aparecida Sadae Tanaka Maria Elisa Peichoto |
| author_facet | Marcelo Larami Santoro Ana Teresa Azevedo Sachetto Jaqueline Gomes Rosa Ricardo José Soares Torquato Débora Andrade-Silva Dilza Trevisan-Silva Cynthia Zaccanini de Albuquerque Solange M. T. Serrano Vânia Gomes de Moura Mattaraia Aparecida Sadae Tanaka Maria Elisa Peichoto |
| author_sort | Marcelo Larami Santoro |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5ea35fb917ad428e82b6dbdbe54a32a4 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-5ea35fb917ad428e82b6dbdbe54a32a42025-01-05T12:25:02ZengNature PortfolioScientific Reports2045-23222024-12-0114111710.1038/s41598-024-81851-8Jararaca GPIb-binding protein causes thrombocytopenia during Bothrops jararaca envenomationMarcelo Larami Santoro0Ana Teresa Azevedo Sachetto1Jaqueline Gomes Rosa2Ricardo José Soares Torquato3Débora Andrade-Silva4Dilza Trevisan-Silva5Cynthia Zaccanini de Albuquerque6Solange M. T. Serrano7Vânia Gomes de Moura Mattaraia8Aparecida Sadae Tanaka9Maria Elisa Peichoto10Biotério Central, Instituto ButantanBiotério Central, Instituto ButantanBiotério Central, Instituto ButantanDepartmento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP)Laboratório de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Instituto ButantanLaboratório de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Instituto ButantanBiotério Central, Instituto ButantanLaboratório de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Instituto ButantanBiotério Central, Instituto ButantanDepartmento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP)Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)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.https://doi.org/10.1038/s41598-024-81851-8Blood plateletsThrombocytopeniaSnaclecC-type lectin-like proteinsGlycoprotein Ib-binding proteinFibrinogen |
| spellingShingle | Marcelo Larami Santoro Ana Teresa Azevedo Sachetto Jaqueline Gomes Rosa Ricardo José Soares Torquato Débora Andrade-Silva Dilza Trevisan-Silva Cynthia Zaccanini de Albuquerque Solange M. T. Serrano Vânia Gomes de Moura Mattaraia Aparecida Sadae Tanaka Maria Elisa Peichoto Jararaca GPIb-binding protein causes thrombocytopenia during Bothrops jararaca envenomation Scientific Reports Blood platelets Thrombocytopenia Snaclec C-type lectin-like proteins Glycoprotein Ib-binding protein Fibrinogen |
| title | Jararaca GPIb-binding protein causes thrombocytopenia during Bothrops jararaca envenomation |
| title_full | Jararaca GPIb-binding protein causes thrombocytopenia during Bothrops jararaca envenomation |
| title_fullStr | Jararaca GPIb-binding protein causes thrombocytopenia during Bothrops jararaca envenomation |
| title_full_unstemmed | Jararaca GPIb-binding protein causes thrombocytopenia during Bothrops jararaca envenomation |
| title_short | Jararaca GPIb-binding protein causes thrombocytopenia during Bothrops jararaca envenomation |
| title_sort | jararaca gpib binding protein causes thrombocytopenia during bothrops jararaca envenomation |
| topic | Blood platelets Thrombocytopenia Snaclec C-type lectin-like proteins Glycoprotein Ib-binding protein Fibrinogen |
| url | https://doi.org/10.1038/s41598-024-81851-8 |
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