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Doctoral Thesis
DOI
10.11606/T.42.2013.tde-16062014-084306
Document
Author
Full name
Fernanda Bredariol Velhote
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Cury, Yara (President)
Antunes, Edson
Hyslop, Stephen
Starobinas, Nancy
Vessoni, Sandra Coccuzzo Sampaio
Title in Portuguese
Caracterização da ação da crotalfina sobre a função de macrófagos peritoneais de ratos.
Keywords in Portuguese
Fagocitose
Inflamação
Macrófagos
Peptídeos
Ratos
Abstract in Portuguese
Crotalfina (CRF) é um peptídeo produzido do veneno da serpente Crotalus durissus terrificus com efeito antinociceptivo tipo opióide detectado apenas na presença de inflamação. Estudos sobre mecanismos de analgesia relatam a ação de opióides em células imunes e macrófagos são apontados como alvos para os efeitos destes. Este estudo caracterizou a ação da CRF sobre funções de macrófagos e avaliou a importância de seus receptores opióides nestas ações. Os resultados indicam que CRF inibe fagocitose, liberação de H2O2 e produção de NO e TNF-a, modula IL-6 e estimula IL-1b por macrófagos residentes e inflamatórios. Ensaios de expressão e ativação mostram que macrófagos residentes expressam receptores opióides k seguido de m e d e macrófagos inflamatórios expressam receptores m seguido de k e d. A CRF interferiu, de maneira distinta, com a expressão destes receptores, dependendo do estado de ativação destas células. Antagonistas destes receptores bloquearam a ação da CRF, mostrando que este peptídeo possui ação imunomodulatória mediada por receptores opióides.
Title in English
Characterization of crotalphine actions on function of rat macrophages.
Keywords in English
Inflammation
Macrophages
Peptides
Phagocytosis
Rats
Abstract in English
Crotalphine (CRF) is a peptide isolated from the venom of Crotalus durissus terrificus with type opioid antinociceptive effect only detected in the presence of inflammation. Studies on mechanisms of analgesia reported the action of opioids in immune cells and macrophages are considered as targets for these effects. This study characterized the action of CRF on functions of macrophages and assessed the importance of opioid receptors in these actions. The results indicate that CRF inhibits phagocytosis, release of H2O2 and production of NO and TNF-a, modulates IL-6 and stimulates IL-1b production by resident and inflammatory macrophages. Expression and activation assays show that resident macrophages express k receptors followed by m and d. Inflammatory macrophages express m receptors followed by k and d. CRF interfered differently with the expression of these receptors, depending on the activation state of these cells. Antagonists of these receptors blocked the action of CRF, showing that this peptide has immunomodulatory action mediated by opioid receptors.
 
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Release Date
2018-06-16
Publishing Date
2014-06-17
 
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