Comparative study of platelet aggregation and secretion induced by Bothrops jararaca snake venom and thrombin

Autor(es)

Rosa, Jaqueline Gomes ^{[1, 2]} ; de Albuquerque, Cynthia Zaccanini ^[3] ; de Moura Mattaraia, Vania Gomes ^[3] ; Santoro, Marcelo Larami ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Sao Paulo, SP - Brazil

^[2] Inst Butantan, Lab Fisiopatol, Av Dr Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil

^[3] Inst Butantan, Bioterio Cent, Av Dr Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 159, p. 50-60, MAR 1 2019.
• Citações Web of Science: 1

Resumo

Victims of Bothrops jararaca snakebites manifest bleedings, blood incoagulability, platelet dysfunction, and thrombocytopenia, and the latter has been directly implicated in the genesis of hemorrhagic diathesis. We addressed herein the direct effects of B. jararaca venom (BjV) on ex vivo platelet aggregation and granule secretion in washed human and mouse platelets. BjV directly aggregated platelets, but the extent of platelet aggregation was lower in human than mouse platelets. On the other hand, BjV (24.4 mu g/mL) and thrombin (0.1 U/mL) induced a similar extent of ATP and platelet factor 4 (PF4) secretion in both species. BjV-induced platelet aggregation was independent of the platelet dense body content, as in pearl mouse (Ap3b1(-/-))platelets, whose dense bodies are deficient in adenine nucleotides and serotonin, the extent of platelet aggregation was superior to that induced in BALB/c or C57BL/6 mice. BjV-induced beta-hexosaminidase secretion in human platelets was less intense than that evoked by thrombin, and the contrary was observed in mouse platelets. Irreversible inactivation of platelet cyclooxygenase 1 by acetylsalicylic acid did not reduce BjV-induced platelet aggregation. BjV exerted no cytotoxic activity in human and mouse platelets, as evaluated by lactate dehydrogenase loss. Eptifibatide, which inhibits the binding of fibrinogen to platelet glycoprotein complex GPIIb-IIIa, differently blocked BjV-induced platelet aggregation in mice and humans. BjV-induced platelet aggregation did not depend on snake venom serine proteinases nor metalloproteinases in mice, whilst serine proteinases were rather important for platelet aggregation in humans. Our results show that BjV induces direct activation, aggregation, and secretion in human and mouse platelets, but it exerts diverse responses in them, which should be considered in comparative studies to understand pathophysiological events during Bothrops envenomation. (AU)

• Processo FAPESP: 18/07819-9 - 64th Annual Scientific and Standardization Committee (SSC) Meeting of the ISTH
• Beneficiário: Marcelo Larami Santoro
• Modalidade de apoio: Auxílio à Pesquisa - Reunião - Exterior
• Processo FAPESP: 13/25177-0 - Envolvimento do fator de Von Willebrand nos distúrbios hemostáticos do envenenamento pela serpente Bothrops jararaca: estudo experimental
• Beneficiário: Marcelo Larami Santoro
• Modalidade de apoio: Auxílio à Pesquisa - Regular