Published ahead of print on June 9, 2005, doi:10.1165/rcmb.2005-0145OC Am. J. Respir. Cell Mol. Biol., Volume 33, Number 3, September 2005, 254-261 A more recent version of this article appeared on September 1, 2005
Submitted on April 18, 2005 Allergic Challenge-Elicited Lipid Bodies Compartmentalize In Vivo LTC4 Synthesis within EosinophilsAdriana Vieira-de-Abreu1,1 Departamento de Fisiologia e Farmacodinamica, Instituto Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil, 2 Department of Medicine, Harvard Medical School, Boston, MA, USA * To whom correspondence should be addressed. E-mail: pbozza{at}ioc.fiocruz.br.
Eosinophils are an important source of LTC4, which can be synthesized within lipid bodies - cytoplasmic organelles where eicosanoid formation may take place. Allergy-driven lipid body formation and function have never been investigated. Here, we studied the in vivo induction and role of lipid bodies within eosinophils recruited to sites of allergic inflammation. Using two murine models of allergic inflammation (asthma and pleurisy), we verified that parallel to the eosinophil influx, allergic challenge also induced lipid body formation within recruited eosinophils. Neutralizing antibodies to eotaxin/CCL11, RANTES/CCL5 or CCR3 partially inhibited lipid body formation within recruited eosinophils in allergic pleurisy model. Likewise, intrapleural administration of RANTES or eotaxin also induced significant influx of eosinophils loaded with lipid bodies. By immuno-labeling, 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 immuno-localization of newly formed LTC4 demonstrated that lipid bodies were the sites of formation of this eicosanoid within infiltrating eosinophils. Therefore, allergic inflammation triggers in vivo formation of new lipid bodies within infiltrating eosinophils, a phenomenon largely mediated by eotaxin/RANTES acting via CCR3 receptors. Such in vivo allergen-driven lipid bodies function as intracellular compartments of LTC4 synthesis.
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