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Doctoral Thesis
DOI
10.11606/T.5.2008.tde-10032008-154254
Document
Author
Full name
Fernanda Magalhães Arantes Costa
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Martins, Milton de Arruda (President)
Lima, Wothan Tavares de
Sato, Maria Notomi
Silva, Carla Lima da
Tibério, Iolanda de Fátima Lopes Calvo
Title in Portuguese
Efeitos do resíduo da queima de óleo diesel (ROFA) e da inflamação pulmonar alérgica crônica em três linhagens de camundongos
Keywords in Portuguese
Asma
Camundongos.
Inflamação pulmão
Material particulado
Modelos animais
Mucosa respiratória
Reatividade brônquica
Abstract in Portuguese
Neste estudo, foram realizados três experimentos distintos (1) analisando os efeitos da administração de material particulado em camundongos BALB/c com inflamação pulmonar alérgica crônica induzida por ovalbumina; (2) comparando camundongos AIRmax e AIRmin com inflamação pulmonar alérgica crônica induzida por ovalbumina; (3) comparando camundongos AIRmax e AIRmin que receberam material particulado (resíduo da queima de óleo diesel - ROFA) por via intranasal. Para a indução da inflamação pulmonar alérgica crônica, os camundongos foram sensibilizados com ovalbumina (OVA) através de duas injeções intraperitoneais de alérgeno com o adjuvante hidróxido de alumínio (dias 0 e 14) e quatro inalações de OVA 1% (dias 22, 24, 26 e 28). Os animais que foram expostos ao material particulado, receberam ROFA (60 ?g) nos dias 0, 2, 4 e 6 no experimento do efeito do material particulado ou nos dias dos desafios com OVA no experimento do efeito da administração de material particulado em animais com inflamação pulmonar induzida pela OVA. Os grupos controle foram tratados com solução salina 0,9 % seguindo o mesmo protocolo. Quarenta e oito horas após o último desafio, a responsividade pulmonar foi medida por broncoprovocação àr metacolina através da pletismografia de corpo inteiro, após a qual os animais foram sacrificados e tiveram os pulmões removidos para analise histológica. O estudo realizado com animais BALB/c para análise dos efeitos do material particulado sobre a resposta inflamatória induzida pela ovalbumina mostrou um aumento de responsividade nos animais inflamados e co-expostos ao material particulado, sem efeito sobre a inflamação ou remodelamento epitelial induzidos pela OVA. A exposição ao material particulado por si só levou a uma diminuição da área ocupada por células ciliadas e a um aumento da responsividade pulmonar. O experimento realizado com camundongos das linhagens AIRmax e AIRmin para estudar eventuais diferenças entre a resposta destas linhagens à inflamação pulmonar crônica induzida pela OVA mostrou uma maior susceptibilidade dos animais AIRmin, com maior infiltrado eosinofílico nas vias aéreas e responsividade pulmonar. Por outro lado, o estudo realizado para verificar a ação do material particulado nas linhagens AIRmax e AIRmin mostrou um intenso remodelamento epitelial, com infiltrado macrofágico ao redor das vias aéreas de ambas as linhagens, porém os animais AIRmin apresentaram maior responsividade pulmonar que os AIRmax quando expostos ao material particulado. Assim pudemos concluir que (1) a exposição ao material particulado na presença de inflamação pulmonar alérgica crônica amplifica o remodelamento epitelial e a responsividade pulmonar; o background genético influencia (2) a inflamação eosinofílica e a responsividade pulmonar induzidas pela inflamação alérgica crônica bem como (3) a responsividade pulmonar induzida pela exposição ao material particulado.
Title in English
Effects of residual diesel oil fly ash (ROFA) and pulmonary allergic chronic inflammation in tree lines of mice
Keywords in English
Animal models
Asthma
Bronchial hyperreactivity
Inflammation
Lung
Mice.
Particulate matter
Respiratory mucosa
Abstract in English
In this study, three distinct experiments were performed (1) examining the effects of administration of particulate matter in BALB/c mice with chronic allergic pulmonary inflammation induced by ovalbumin; (2) comparing AIRmax and AIRmin mice with chronic allergic pulmonary inflammation induced by ovalbumin; (3) comparing AIRmax and AIRmin mice receiving particulate matter (residue from the burning of diesel oil - ROFA) intranasally. For the induction of chronic allergic pulmonary inflammation, the mice were sensitized to ovalbumin (OVA) through two intraperitoneal injections of allergen with adjuvant aluminum hydroxide (days 0 and 14) and four inhalations of OVA 1% (days 22, 24, 26 and 28). The animals that were exposed to particulate matter received ROFA (60 ?g) on days 0, 2, 4 and 6 in the study of the effect of the particulate matter or after the challenges with OVA in experiment of the effect of administration of particulate matter in animals with pulmonary inflammation induced by OVA. The control groups were treated with saline 0.9% following the same protocol. Forty eight hours after the last challenge, pulmonary responsiveness was measured through broncoprovocation to methacholine by whole body plethysmography, after which the animals were sacrificed and the lungs were removed for histologic analysis. The study conducted on animals BALB/c for analysis of the effects of particulate matter on the inflammatory response induced by ovalbumin showed an increase of responsiveness in animals with allergic inflammation and exposed to the particulate matter, without effects on inflammation or epithelial remodeling induced by OVA. Exposure to particulate matter led to a reduction in the area occupied by ciliated cells and increased lung responsiveness. The experiment in AIRmax AIRmin mice to study possible differences in the response of these strains to chronic lung inflammation induced by OVA showed greater susceptibility of AIRmin, with more eosinophilic infiltration in airway and greater lung responsiveness. The study to check the action of particulate matter in the lines AIRmax and AIRmin showed an intense epithelial remodeling, with macrophagic infiltrate around the airways of both strains. However, AIRmin mice had higher pulmonary responsiveness than AIRmax when exposed to particulate matter. We conclude that (1) exposure to particulate matter in the presence of chronic allergic pulmonary inflammation amplifies the epithelial remodeling and pulmonary responsiveness; the genetic background influences (2) the pulmonary responsiveness and eosinophilic inflammation induced by chronic allergic inflammation and (3) the pulmonary responsiveness induced by exposure to particulate matter.
 
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Publishing Date
2008-03-17
 
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