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Mémoire de Maîtrise
DOI
10.11606/D.42.2009.tde-09022010-120747
Document
Auteur
Nom complet
Marlos Cortez Sampaio
Unité de l'USP
Domain de Connaissance
Date de Soutenance
Editeur
São Paulo, 2009
Directeur
Jury
Teixeira, Catarina de Fatima Pereira (Président)
Mauro, Eliana Faquim de Lima
Sampaio, Sandra Coccuzzo
Titre en portugais
Estudo do componente leucocitário e de mediadores quimiotáticos da reação inflamatória induzida pelo veneno de Bothrops moojeni. Participação de mastócitos e da histamina no recrutamento leucocitário
Mots-clés en portugais
Bothrops moojeni
Histamina
Inflamação
Leucócitos
Mastócitos
Mediadores quimiotáticos
Resumé en portugais
Este estudo teve por objetivos: a) caracterizar o influxo de leucócitos (LC) induzido pelo veneno de Bothrops moojeni (VBm); b) avaliar o papel dos mastócitos (MC) e da histamina neste evento; c) analisar a liberação de TXA2, PGD2, LTB4, MCP-1 e KC e d) avaliar a capacidade do VBm desgranular MC in vivo e in vitro. A injeção intraperitoneal de VBm, em camundongos, causou o recrutamento de LC e neutrofilia. O tratamento dos animais com cromoglicato aboliu o influxo de LC enquanto a difenidramina, ranitidina e a tioperamida, antagonistas da histamina, reduziram o influxo de neutrófilos. Ainda, o veneno induziu a liberação de PGD2, TXA2, LTB4, MCP-1 e de KC e causou a desgranulação de MC in vivo e a liberação de -hexosaminidase de MC in vitro. Em conclusão, o VBm induz influxo de LC para o local de sua injeção. Este efeito depende da histamina, via receptores H1, H2 e H4 e da desgranulação de MC, que decorre de ação direta do veneno nestas células. A neutrofilia e o TXA2, LTB4, MCP-1 e KC devem contribuir para o influxo de leucócitos causado pelo VBm.
Titre en anglais
Studies on the leukocyte component and chemotactic mediators of the inflammatory reaction induced by Bothrops moojeni venom. Participation of mast cells and histamine in leukocyte recruitment.
Mots-clés en anglais
Bothrops moojeni
Chemotactic mediators
Histamine
Inflammation
Leukocytes
Mast cells
Resumé en anglais
In this study the effects of Bothrops moojeni venom (BmV) on the cellular component of inflammatory responses and the mechanisms involved in this effect were investigated. The effects of venom on peritoneal and circulating leukocyte numbers and on the release of inflammatory mediators, such as LTB4, TXA2, PGD2, MIP-1 and KC, were assessed. The role of both mast cells and histamine receptors in leukocyte recruitment induced by BmV was assessed by selected pharmacological treatments. BmV caused a marked infiltration of leukocytes (3-24 h) when injected into the peritoneal cavity of mice. Neutrophils (PMN) were the predominant cell type in the early stages of response whereas macrophages (MN) were accumulated from 3 up to 24 h. Moreover, BmV increased blood neutrophil numbers at 3 h after injection. The BmV-induced leukocyte influx was abrogated by cromoglicate and significantly reduced either by difenidramine or ranitidine or tioperamide, histamine H1, H2 and H4 receptor antagonists, respectively, at 6 h after injection. Significant increments in peritoneal levels of LTB4, TXA2, PGD2, MIP-1 and KC were detected at distinct periods of time after venom injection. In addition, BmV induced mast cell degranulation both in vivo and in vitro. In conclusion, obtained data demonstrated the ability of BmV induce leukocyte recruitment into the site of its injection. This effect is dependent on mast cell activation and degranulation, which may be due to a direct effect of venom on these cells, and is mediated at least in part by histamine via H1, H2 and H4 receptors. Moreover, the ability of venom to mobilize leukocytes from bone marrow reserve compartments and to release the chemotactic mediators TXA2, LTB4, MCP-1 and KC may be relevant for leukocyte infiltration.
 
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Date de Publication
2010-03-15
 
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