Scholarship 08/00931-6 - Hipersensibilidade, Asma - BV FAPESP
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Effect of the pre-exposure the enterotoxins staphylococcal on the eosinophil lung recruitment in model murino of the allergic

Grant number: 08/00931-6
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Start date until: May 01, 2008
End date until: April 30, 2009
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal Investigator:Edson Antunes
Grantee:Giovana Gomes
Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The selective recruitment and activation of eosinophils into the bronchial mucosa are considered key events in the pathogenesis of bronchial asthma, a progressive chronic inflammatory disease that accounts for high health care costs in the world. Accordingly, there is a positive correlation between the degree of eosinophilia in peripheral blood (and in bronchoalveolar lavage fluid) and bronchial hyperresponsiveness with the disease severity. The Staphyloccocal enterotoxins are proteins produced and secreted by the gram-positive bacterium Staphylococcus aureus, and are responsible for most of the pathological conditions seen in infections caused by S. aureus, including the pulmonary infections. Recent studies from our group showed that staphylococcal enterotoxin type A (SEA) and type B (SEB), given intratracheally to rats, are able to induce a marked pulmonary inflammation characterized by an extensive neutrophil influx that is maximum at 4 h after exposure. This response was associated with the release of cyclooxygenase-e (COX-2) and lypoxygenase metabolites, together with nitric oxide (NO), tumor necrosis factor-± (TNF-±) and interleukin-6 (IL-6) (DESOUZA et al., 2005, 2006). Interestingly, studies have reported a correlation between levels of IgE antibodies to staphylococcal enterotoxins and exacerbation of respiratory diseases, including allergic asthma. However, little is known about the mechanisms underlying such inflammatory exacerbation in asthmatic individuals under exposure to staphylococcal enterotoxins. Approximately two years ago, we initiated a research project looking at the mechanisms involved in the exacerbation of the allergic pulmonary response (particularly the eosinophil infiltration in bronchoalveolar lavage fluid) in rats pre-exposed to SEA and SEB. This project has been largely conducted by the FAPESP fellowship Nadia S. Mariano as a Master thesis (No.06/54104-8). At present, we have showed that pre-exposure to SEA exacerbates the eosinophil infiltration in the bronchoalveolar lavage fluid at 24 h post-ovalbumin challenge. However, at the same time that this experimental model in rats seems to mimic the clinical conditions thus functioning as a good pharmacological strategy to answer our question, we are dealing with difficulties in progressing this project, mainly because there are no commercial available kits for key mediators produced in rats such as IgE, cytokines, adhesion molecules, amongst others. Therefore, we aim to test our model in mice (pre-exposure to SEA and SEB and further allergenic challenge). In general, our goal is to investigate in mice the allergic pulmonary responses after pre-exposure of animals to SEA and SEB. Initially, we are exploring different doses of SEA (or SEB) and different pre-exposure time prior to ovalbumin challenge and quantifying the total and differential leukocyte counts in the bronchoalveolar lavage fluid, peripheral blood and bone marrow. Whether data in mice are encouraging, in a second phase of the study, the mechanisms involved in the exacerbation of allergic pulmonary responses (SEA/SEB vs. ovalbumin challenge) will be explored, by measuring the levels of Th1 (TNF-± e IFN-g) and Th2 (IL-4, IL-5, IL-6, IL-10 and eotaxin) mediators, as well as of IgE in bronchoalveolar lavage fluid and/or serum. Morphological lung analysis and mucus production may also be carried out in parallel with the functional and biochemical study.

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