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Doctoral Thesis
DOI
10.11606/T.42.2016.tde-12092016-113750
Document
Author
Full name
Marie Paule Jacqueline Delafontaine
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Tambourgi, Denise Vilarinho (President)
Câmara, Niels Olsen Saraiva
Grumach, Anete Sevciovic
Medeiros, Carlos Roberto de
Portaro, Fernanda Calheta Vieira
Title in Portuguese
Veneno da serpente Bothrops lanceolatus: caracterização, ativação do sistema complemento e mecanismos potenciais envolvidos no envenenamento.
Keywords in Portuguese
Bothrops lanceolatus
Anafilatoxinas
Inflamação
Sistema complemento
Soro antibotrópico
Veneno de serpente
Abstract in Portuguese
Na Martinica, os envenenamentos por Bothrops lanceolatus apresentam um quadro clínico trombótico, acompanhado de inflamação local extensa, envolvendo edema, dor e hemorragia limitada. Neste estudo foi mostrado que vários componentes do veneno compartilham similaridades antigênicas com venenos de espécies da América do Sul. O veneno de B. lanceolatus é citotóxico para queratinócitos e células endoteliais, induzindo a produção de citocinas e quimiocinas pro-inflamatórias pelas células. O veneno de B. lanceolatus ativa a cascata do complemento, liberando anafilatoxinas, assim como o complexo terminal do complemento. Ele apresenta uma ação proteolítica sobre os componentes purificados C3, C4, C5, e o inibidor de C1, C1-INH. O veneno também desequilibra o balanço de expressão dos reguladores do complemento na membrana das células endoteliais. Estes dados demonstram que o veneno de B. lanceolatus exibe uma potente ação proinflamatória, pela ativação do sistema complemento e pela sua toxicidade em células endoteliais.
Title in English
Bothrops lanceolatus snake venom: characterization, activation of the complement system and potential mechanisms involved in envenoming.
Keywords in English
Bothrops lanceolatus
Anaphylatoxins
Antibothropic antivenom
Complement system
Inflammation
Snake venom
Abstract in English
In Martinique envenomations by Bothrops lanceolatus are characterized by a systemic thrombotic syndrome and important local inflammation, involving oedema and pain, but limited haemorrhage. In this study, we show that several components of B. lanceolatus venom share antigenic similarities with South American Bothrops species. Still, B. lanceolatus venom proteases present substrate specificity. The venom is cytotoxic for keratinocytes and endothelial vascular cells, inducing the production of pro-inflammatory cytokines and chemokines. B. lanceolatus venom activates the complement cascade, releasing anaphylatoxins and the terminal complement complex. It also shows a direct proteolytic activity upon the purified complement proteins C3, C4, C5, and the inhibitor of C1, C1-INH. B. lanceolatus venom modified the balance of complement regulators on endothelial cells membrane. In conclusion, B. lanceolatus venom displays important pro-inflammatory properties, as it activates the complement cascade and impacts endothelial cells.
 
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Release Date
2018-09-12
Publishing Date
2016-09-12
 
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