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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Involvement of von Willebrand factor and botrocetin in the thrombocytopenia induced by Bothrops jararaca snake venom

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Thomazini, Camila Martos [1, 2] ; Sachetto, Ana Teresa Azevedo [1, 2] ; de Albuquerque, Cynthia Zaccanini [3] ; de Moura Mattaraia, Vania Gomes [3] ; de Oliveira, Ana Karina [4] ; Serrano, Solange Maria de Toledo [4] ; Lebrun, Ivo [5] ; Barbaro, Katia Cristina [6] ; Santoro, Marcelo Larami [1, 2]
Total Authors: 9
[1] Inst Butantan, Lab Fisiopatol, Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Fac Med, Programa Posgrad Clin Med, Sao Paulo, SP - Brazil
[3] Inst Butantan, Bioterio Cent, Sao Paulo, SP - Brazil
[4] Inst Butantan, Ctr Toxins Immune Response & Cell Signaling CeTIC, Lab Toxinol Aplicada, Sao Paulo, SP - Brazil
[5] Inst Butantan, Lab Bioquim & Biofis, Sao Paulo, SP - Brazil
[6] Inst Butantan, Lab Imunopatol, Sao Paulo, SP - Brazil
Total Affiliations: 6
Document type: Journal article
Source: PLoS Neglected Tropical Diseases; v. 15, n. 9 SEP 2021.
Web of Science Citations: 0

Author summary Envenomation by snakebites is a major burden to tropical and subtropical areas in the world. Many snake species produce venoms that, when injected into victims, cause bleedings and other associated symptoms and signs. This work aimed to understand the mechanisms that lead to a fall in blood platelet counts after bites by a snake that inhabits in southeastern Brazil, the lance-headed snake Bothrops jararaca (popularly known as jararaca). We used experimental approaches to understand the involvement of a protein from jararaca venom, called botrocetin, and a protein present in our blood (von Willebrand factor) in the fall of platelet counts. We observed that botrocetin alters von Willebrand factor, but this mechanism in not important for the decrease in platelet counts. We show that jararaca snake venom disturb blood platelets in a complex and intricate way, and that other venom compounds are involved in the decrease of platelet counts during snakebite envenomation. Patients bitten by snakes consistently manifest a bleeding tendency, in which thrombocytopenia, consumption coagulopathy, mucous bleeding, and, more rarely, thrombotic microangiopathy, are observed. Von Willebrand factor (VWF) is required for primary hemostasis, and some venom proteins, such as botrocetin (a C-type lectin-like protein) and snake venom metalloproteinases (SVMP), disturb the normal interaction between platelets and VWF, possibly contributing to snakebite-induced bleedings. To understand the relationship among plasma VWF, platelets, botrocetin and SVMP from Bothrops jararaca snake venom (BjV) in the development of thrombocytopenia, we used (a) Wistar rats injected s.c. with BjV preincubated with anti-botrocetin antibodies (ABA) and/or Na-2-EDTA (a SVMP inhibitor), and (b) VWF knockout mice (Vwf(-/-)) injected with BjV. Under all conditions, BjV induced a rapid and intense thrombocytopenia. In rats, BjV alone reduced the levels of VWF:Ag, VWF:CB, high molecular weight multimers of VWF, ADAMTS13 activity, and factor VIII. Moreover, VWF:Ag levels in rats that received BjV preincubated with Na-2-EDTA and/or ABA tended to recover faster. In mice, BjV caused thrombocytopenia in both Vwf(-/-) and C57BL/6 (background control) strains, and VWF:Ag levels tended to decrease in C57BL/6, demonstrating that thrombocytopenia was independent of the presence of plasma VWF. These findings showed that botrocetin present in BjV failed to affect the extent or the time course of thrombocytopenia induced by envenomation, but it contributed to decrease the levels and function of plasma VWF. Thus, VWF alterations during B. jararaca envenomation are an ancillary event, and not the main mechanism leading to decreased platelet counts. (AU)

FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
Grantee:Hugo Aguirre Armelin
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 18/26015-8 - Novel mechanisms of pathogenesis of Sepsis and Bothrops envenomation: potential of rutin as a therapeutic agent
Grantee:Ana Teresa Azevedo Sachetto
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 13/20239-8 - Disturbances of Von Willebrand factor and hepatic synthesis of hemosthatic factors induced by experimental Bothrops jararaca envenomation
Grantee:Camila Martos Thomazini
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 19/07618-6 - Hemostasis-inflammation interaction during envenomation by Bothrops jararaca snakes: pathogenesis of thrombocytopenia, and therapeutic anti-ophidian mechanisms of quercetin-3-rutinoside (rutin)
Grantee:Marcelo Larami Santoro
Support Opportunities: Regular Research Grants
FAPESP's process: 13/25177-0 - Involvement of Von Willebrand factor in hemostatic disturbances induced by Bothrops jararaca snake venom: experimental study
Grantee:Marcelo Larami Santoro
Support Opportunities: Regular Research Grants