Resposta comparativa pleural "in vivo" e do mesotélio "in vitro" à exposição por diferentes fibras de asbesto / Comparison of in vivo pleural response and in vitro mesothelial response to different asbestos fibers

AUTOR(ES)
DATA DE PUBLICAÇÃO

2006

RESUMO

Asbestos-derived products are used thoroughly by industry. Several diseases related to asbestos exposition have been described, among them the primary tumor of the pleura mesothelioma. The mechanisms by which asbestos fibers produce injury to the pleural space are not clear. Among the factors possibly implicated are the effects secondary to an inflammatory response characterized by cellular migration and the release of molecular mediators leading to necrosis, apoptosis, cellular proliferation and fibrogenesis. However, it is difficulty to characterize the cellular response in vivo, mainly by virtue of the multi-cellular population present into the pleural cavity. Therefore, studies involving animals genetically modified or genetically selected have been proposed in the literature, in order to better understand the role of the several cellular populations involved in this complex process. In this study, our objective was to determine the inflammatory response of the pleural fluid and compare to the response of cultured mesothelial cells exposed to different asbestos fibers. Controls and mice genetically selected for high (AIR max) or low (AIR min) inflammatory response as well as mice cultured mesothelial cells were treated to crocidolite or chrysotile asbestos fibers. After 4, 24 or 48 hours the production of the cytokines IL-1b, IL-6 and MIP-2 were analyzed. In addition, the in vivo cellular profile of the pleural fluid and the Ra PDGF expression in the pleura fragments was documented. In parallel, the in vitro mesothelial cellular response of apoptosis and necrosis was quantified. Both asbestos fibers produced in AIR max mice a significant elevation in the pleural fluid total leukocytes, neutrophils and IL-1b levels in comparison to the controls and AIR min animals. However, no difference was found in the macrophage number, IL-6 and MIP-2 levels. Cultured mesothelial cells had a high apoptosis, necrosis, IL-1b, IL-6 and MIP-2 levels in comparison to the controls when exposed to either crocidolite or chrysotile. MIP-2 and IL-1b levels in cultured mesothelial cells strongly correlated with the levels of the pleural fluid for both fibers. In addition, a pronounced expression of Ra PDGF in the pleural surface was demonstrated in both high and low inflammatory selected mice when compared to the controls. In conclusion, we characterized the acute inflammatory response to the asbestos fibers crocidolite and chrysotile in an in vivo and in vitro experimental model, aiming to contribute to better understand the mechanism of cellular aggression secondary to this particulate material of such frequent commercial use.

ASSUNTO(S)

amiantos serpentinas inflamação mesothelioma crocidolite asbestos serpentine asbestos inflammation amianto crocidolita animal models mesotelioma apoptosis apoptose modelos animais

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