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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2016.tde-12092016-150015
Document
Author
Full name
Lygia Samartin Gonçalves Luchini
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Tambourgi, Denise Vilarinho (President)
Baptistão, Carla Cristina Squaiella
Nunes, Anderson de Sá
 
Title in Portuguese
Papel do sistema complemento no processo inflamatório causado por uma metaloproteinase de classe PI, do veneno da serpente Bothrops pirajai: análise em modelo ex vivo de sangue total humano.
Keywords in Portuguese
Bothrops pirajai
Inflamação
Metaloproteinase
Sangue total humano
Sistema complemento
Abstract in Portuguese
O veneno de serpentes do gênero Bothrops (responsáveis por 80% dos envenenamentos no Brasil) é composto por metalo e serinoproteases, disintegrinas, fosfolipases, entre outros, e pode causar edema, hemorragia, necrose, e manifestações sistêmicas, como coagulação intravascular, choque, falência renal e hemorragia. O veneno da B. pirajai ativa o sistema complemento (C), sugerindo uma contribuição para o agravamento dos sintomas. Considerando a importância do C no processo inflamatório e o papel das metaloproteinases nos envenenamentos, verificou-se que o tratamento do sangue total humano (onde células e mediadores plasmáticos interagem entre si) com ou sem a compstatina (inibidor de C3 do C), e com a metaloproteinase de classe PI do veneno de B. pirajai, levou a diferenças bastante significativas na expressão dos marcadores analisados nos leucócitos, na geração de anafilatoxinas e TCC, e na quantificação de citocinas e quimiocinas no plasma, sugerindo que a inibição do C reduz o processo inflamatório, podendo ser uma terapia efetiva para envenenamentos botrópicos.
 
Title in English
Role of the complement system in the inflammatory process caused by a class P1 metalloproteinase from Bothrops pirajai venom: Analysis in the ex vivo model of human whole blood.
Keywords in English
Bothrops pirajai
Complement system
Human whole blood
Inflammation
Metalloproteinase
Abstract in English
The snake venom of Bothrops genus (responsible for 80% of envenomation in Brazil) is composed by metallo and serine proteases, disintegrins, phospholipase, among others, and can cause edema, hemorrhage, necrosis, and systemic manifestations, such as intravascular coagulation, shock, renal failure and systemic hemorrhage. The venom of B. pirajai is able to activate the complement system (C), suggesting a contribution to the worsening of symptoms. Considering the importance of C in the inflammatory process and the role of metalloproteinases in envenomation, it was found that treatment of human whole blood (where cells and plasma mediators interact) with or without compstatin (C3 inhibitor), and with a class PI metalloproteinase from B. pirajai's venom led to highly significant differences in the expression of the markers analyzed in leukocytes, in generation of anaphylatoxins and TCC, and quantification of cytokines and chemokines in plasma, suggesting that inhibition of C reduces the inflammatory process and may be an effective therapy for bothropic envenomations.
 
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Publishing Date
2016-09-12
 
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