Allergic challenge-elicited lipid bodies compartmentalize in vivo leukotriene C4 synthesis within eosinophils.
Eosinophils are an important source of leukotriene (LT)C(4), 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 the allergic pleurisy model. Likewise, intrapleural administration of RANTES or eotaxin also induced significant influx of eosinophils loaded with lipid bodies. 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 LTC(4) 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 LTC(4) synthesis.
Vieira-de-Abreu
Adriana
A
Laboratorio de Imunofarmacologia, Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz; Av. Brasil 4365, Manguinhos 21045-900 Rio de Janeiro, RJ Brazil.
Assis
Edson F
EF
Gomes
Gleice S
GS
Castro-Faria-Neto
Hugo C
HC
Weller
Peter F
PF
Bandeira-Melo
Christianne
C
Bozza
Patrícia T
PT
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D002451:Cell Compartmentation / Q000276:immunology*; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000494:pharmacology; D019742:Chemokines, CC / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004804:Eosinophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005260:Female; D017997:Leukotriene C4 / Q000096:biosynthesis / Q000378:metabolism*; D050356:Lipid Metabolism; D008055:Lipids / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010998:Pleurisy / Q000276:immunology / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019742:Chemokines, CC; D008055:Lipids; D017997:Leukotriene C4; D001094:Arachidonate 5-Lipoxygenase