Lipid bodies in oxidized LDL-induced foam cells are leukotriene-synthesizing organelles: a MCP-1/CCL2 regulated phenomenon

dc.creatorSilva, Adriana R.
dc.creatorPacheco, Patricia
dc.creatorAbreu, Adriana Vieira de
dc.creatorMaya-Monteiro, Clarissa M.
dc.creatorD'Alegria, Barbara
dc.creatorMagalhães, Kelly G.
dc.creatorAssis, Edson F. de
dc.creatorMelo, Christianne Bandeira
dc.creatorFaria Neto, Hugo C. Castro
dc.creatorBozza, Patrícia T.
dc.date2019-01-10T14:06:56Z
dc.date2019-01-10T14:06:56Z
dc.date2009
dc.date.accessioned2023-09-26T20:52:46Z
dc.date.available2023-09-26T20:52:46Z
dc.identifierSILVA, Adriana R. et al. Lipid bodies in oxidized LDL-induced foam cells are leukotriene-synthesizing organelles: a MCP-1/CCL2 regulated phenomenon. Biochimica et Biophysica Acta, v. 1791, p. 1066-1075, 2009.
dc.identifier1388-1981
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/30962
dc.identifier10.1016/j.bbalip.2009.06.004
dc.identifier0006-3002
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8865483
dc.descriptionLipid-laden foam macrophages are emerging as key players in early atherogenesis. Even though cytoplasmic lipid bodies (lipid droplets) are now recognized as organelles with cell functions beyond lipid storage, the mechanisms controlling lipid body biogenesis within macrophages and their additional functions in atherosclerosis are not completely elucidated. Here we studied oxLDL-elicited macrophage machinery involved in lipid body biogenesis as well as lipid body roles in leukotriene (LT) synthesis. Both in vivo and in vitro, oxLDL (but not native LDL) induced rapid assembly of cytoplasmic lipid bodies-bearing ADRP within mice macrophages. Such oxLDL-elicited foamy-like phenotype was a pertussis toxin-sensitive process that depended on a paracrine activity of endogenous MCP-1/CCL2 and activation of ERK. Pretreatment with neutralizing anti-MCP-1/CCL2 inhibited macrophage ADRP protein expression induced by oxLDL. By directly immuno-localizing leukotrienes at their sites of synthesis, we showed that oxLDL-induced newly formed lipid bodies function as active sites of LTB(4) and LTC(4) synthesis, since oxLDL-induced lipid bodies within foam macrophages compartmentalized the enzyme 5-lipoxygenase and five lipoxygenase-activating protein (FLAP) as well as newly formed LTB(4) and LTC(4). Consistent with MCP-1/CCL-2 role in ox-LDL-induced lipid body biogenesis, in CCR2 deficient mice both ox-LDL-induced lipid body assembly and LT release were reduced as compared to wild type mice. In conclusion, oxLDL-driven foam cells are enriched with leukotriene-synthesizing lipid bodies--specialized organelles whose biogenic process is mediated by MCP-1/CCL2-triggered CCR2 activation and ERK-dependent downstream signaling--that may amplify inflammatory mediator production in atherosclerosis.
dc.description2030-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsrestricted access
dc.subjectArteriosclerose
dc.subjectGotículas lípidicas
dc.subjectInflamação
dc.subjectMacrófagos
dc.subjectAtherosclerosis
dc.subjectFoam cell
dc.subjectLipid droplet
dc.subjectLipoxygenase
dc.subjectLeukotriene
dc.subjectInflammation
dc.subjectMCP-1/CCL2
dc.subjectERK
dc.subjectMacrophage
dc.subjectCélulas Espumosas
dc.subjectArteriosclerose
dc.subjectLipoxigenase
dc.subjectLeucotrienos
dc.subjectQuinases Reguladas por Sinal Extracelular
dc.titleLipid bodies in oxidized LDL-induced foam cells are leukotriene-synthesizing organelles: a MCP-1/CCL2 regulated phenomenon
dc.typeArticle


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