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Doctoral Thesis
Full name
Gabriela Campanholle
Knowledge Area
Date of Defense
São Paulo, 2010
Câmara, Niels Olsen Saraiva (President)
Araújo, Ronaldo de Carvalho
Franco, Marcelo de
Lima, Wothan Tavares de
Seguro, Antonio Carlos
Title in Portuguese
O papel do receptor B1 da bradicinina em modelos experimentais de lesão pulmonar aguda direta e indireta.
Keywords in Portuguese
Inflamação pulmonar
Lesão renal
Abstract in Portuguese
A lesão pulmonar aguda é caracterizada por inflamação pulmonar podendo ser induzida diretamente (LPD), por inalação de lipopolissacarídeo (LPS), ou indiretamente (LPI), por mediadores inflamatórios liberados por órgãos distantes após lesão de isquemia e reperfusão (IR). A Bradicinina, mediador inflamatório, pode agir em dois receptores, um constitutivo (B2R), e um induzido por citocinas inflamatórias (B1R). Neste trabalho verificamos o papel do B1R em modelos de LPD e LPI. Em camundongos C57bl/6, a LPD foi induzida por tratamento intra-nasal com LPS, e a LPI foi induzida por 45 minutos de IR renal. Observamos alterações pulmonares em ambos os modelos de lesão 24 horas após o insulto, como aumento de infiltrado celular, hiperreatividade pulmonar à metacolina, aumento de permeabilidade vascular, e citocinas pró-inflamatórias. Bloqueamos o B1R com antagonista e vimos que a lesão pulmonar foi diminuída em ambos os modelos de lesão. Assim, sugerimos que o B1R contribui tanto para a LPD, induzida por LPS, quanto para a LPI, induzida por IR renal.
Title in English
The role of B1 bradykinin receptor in experimental models of direct and indirect acute lung injury.
Keywords in English
Lung inflammation
Renal lesion
Abstract in English
The acute lung injury (ALI) is characterized by lung inflammation and can be induced directly by lipopolysaccharides inhalation, or indirectly, by systemic inflammatory mediators released from distant organs after and ischemia and reperfusion injury (IRI). Bradykinin, an inflammatory mediator, can act in two different receptors; one is constitutive (B2R), whereas the other is induced by inflammatory cytokines (B1R). We aimed to study the role of B1R in models of direct and indirect ALI. Direct ALI was induced by LPS instillation in C57bl/6 mice, while indirect ALI was induced by 45 minutes of renal IRI. In both injuries, 24 hours after insult, animals presented an increase in cellular infiltration, vascular permeability, hyperreactivity to methacholine, and an up-regulation of pro-inflammatory cytokines in lungs. We blocked the B1R using antagonist and observed that the lung injury was attenuated in both injury models. Thus, we suggest that B1R has an important role in the development of both, direct ALI, induced by LPS, and indirect ALI induced by renal IRI.
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