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Exacerbation of allergic pulmonary inflammatory responses by staphylococcal enterotoxin exposure

Grant number: 07/08022-2
Support type:Regular Research Grants
Duration: August 01, 2008 - July 31, 2010
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Edson Antunes
Grantee:Edson Antunes
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Bronchial asthma is a word-wide and highly progressive prevalent disease with high impact on the health system. Asthma is characterized by a chronic inflammatory response in the airways that results in bronchoconstriction due to the local release of a number of inflammatory contractile mediators. Previous studies carried out in humans and animals have shown that recruitment and activation of eosinophils into the bronchial mucosa play a major role in the asthma pathology. 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. More recently, some 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. These 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. The staphylococcal enterotoxins also act as superantigens, and so part of their actions are believed to reflect this immunomodulator effect. 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-a (TNF-a) and interleukin-6 (DESOUZA et al., 2005, 2006). In order to further advance in these studies, we have designed experiments to test the hypothesis that pre-exposure of rats to SEA (or SEB) exacerbates the allergic pulmonary inflammation (with emphasis in the eosinophil recruitment to bronchoalveolar lavage fluid) in rats actively immunized with ovalbumin, and, if so, the mechanisms underlying such phenomenon. At present, our data showed that pre-exposure to SEA markedly enhances the eosinophil influx into the bronchoalveolar lavage fluid at 24 h post-ovalbumin challenge. This finding seems to mimic the clinical conditions, and therefore is a suitable experimental strategy to further explore the mechanisms involved in the exacerbation of allergic airways inflammation in allergic individuals pre-exposed to staphylococcal enterotoxins. (AU)