Extranuclear lipid bodies, elicited by CCR3-mediated signaling pathways, are the sites of chemokine-enhanced leukotriene C4 production in eosinophils and basophils

被引:99
作者
Bandeira-Melo, C [1 ]
Phoofolo, M [1 ]
Weller, PF [1 ]
机构
[1] Harvard Univ, Beth Israel Deaconess Med Ctr, Charles A Dana Res Inst, Harvard Thorndike Labs,Dept Med, Boston, MA 02215 USA
关键词
D O I
10.1074/jbc.M101436200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Eosinophils and basophils, when activated, become major sources of cysteinyl leukotrienes, eicosanoid mediators pertinent to allergic inflammation. We show that the C-C chemokines, eotaxin and RANTES (regulated upon activation normal T cell expressed and secreted), activate eosinophils and basophils for enhanced leukotriene C-4 (LTC4) generation by distinct signaling and compartmentalization mechanisms involving the induced formation of new cytoplasmic lipid body organelles, Chemokine-induced lipid body formation and enhanced LTC4 release were both mediated by CCR3 receptor G protein-linked downstream signaling involving activation of phosphoinositide 3-kinase, extracellular signal-regulated kinases 1 and 2, and p38 mitogen-activated protein kinases. Chemokine-elicited lipid body numbers correlated with increased calcium ionophore-stimulated LTC4 production and as demonstrated by intracellular immunofluorescent localization of newly formed eicosanoid, lipid bodies were the predominant sites of LTC4 synthesis in both chemokine-stimulated eosinophils and chemokine-primed and ionophore-activated eosinophils. Eotaxin and RANTES initiated signaling via phosphoinositide S-kinase and mitogen-activated protein kinases both elicits the formation of lipid body domains and promotes LTC4 formation at these specific extranuclear sites.
引用
收藏
页码:22779 / 22787
页数:9
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