Mechanisms of fomatiom of the Paper of the Lipid Bodies in Eosinophils in the allergic inflammatory response
Lipid bodies are lipid-rich cytoplasmic inclusions, which are candidates to play a major role in the formation of eicosanoid mediators during inflammatory response. Lipid body formation/function in vivo at sites of allergic inflammation were never investigated. Here, we studied lipid body formation in vivo within eosinophils recruited to sites of allergic inflammation. Using the allergic pleurisy we verified that parallel to eosinophil influx (24 h), allergic challenge induced lipid body formation within recruited eosinophils We then studied the regulation of such phenomenon by using neutralizing antibodies against eotaxin, RANTES or CCR3. Both allergen-induced eosinophil influx and lipid body formation were partially inhibited by these treatments. In addition, administration of RANTES or eotaxin also induced significant eosinophil influx and lipid body formation within 6 h. The involvement of MIF in lipid body formation in eosinophils and its impact for lipid mediator production during allergic inflammation was investigated. MIF was able to induce lipid body formation inhuman eosinophils in vitro, a phenomenon that was blocked by the neutralization of the putative MIF receptor CD74. Likewise, in vivo administration of MIF also induced significant influx of eosinophils loaded with lipid bodies. By using the allergic asthma model we observed that the allergic challenge induced parallel to eosinophil influx, increased MIF, eotaxin and CysLts levels in the bronchoalveolar (BAL) fluid and lipid body formation within recruited eosinophils. MIF-/- mice had a markedly reduction of eosinophil infiltration in the lung. The quantification of BAL CysLts and eotaxin revealed a drastic reduction in OVA-challenged MIF-/- mice, indicating a selective regulation of inflammatory mediators by MIF during allergic inflammation. By immunolabeling, we detected the presence of a key enzyme involved in the leukotriene metabolism-5-lipoxygenase-within eosinophil lipid bodies formed in vivo after allergen challenge. Furthermore, specific immunolocalization of newly formed LTC4 demonstrated that lipid bodies were the sites of formation of this eicosanoid within infiltrating eosinophils. Here, we evaluated the anti-allergic properties of a crude extract of the Brazilian bromeliaceae Nidularium procerum, coded N. procerum, focusing on its effects on allergic eosinophilia. By studying allergic pleurisy, we observed that pretreatment with N. procerum reduced pleural eosinophil influx triggered by allergen challenge. N. procerum was also able to reduce lipid body numbers found within infiltrating eosinophils, indicating that N. procerum in vivo is able to affect both migration and activation of eosinophils. These results indicate that N. procerum have an importante function in modulating to induce lipid body formation and synthesis of lipid mediators during allergic inflammatory response.
Advisor:Christianne Bandeira de Melo; Patricia Torres Bozza
School:Faculdades Oswaldo Cruz
Source Type:Master's Thesis
Keywords:Eosinophils Allergic Inflammatory Response Immune System Lipid Bodies Asthma
Date of Publication:08/04/2006