Leptin Elicits LTC4 Synthesis by Eosinophils Mediated by Sequential Two-Step Autocrine Activation of CCR3 and PGD2 Receptors
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/31244 |
Resumo: | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. |
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Amorim, Natália R. T.Gomes, Tatiana LunaAlmeida, Marcos GamaAlmeida, Glaucia SouzaCanetti, ClaudioDiaz, Bruno L.Weller, Peter F.Bozza, Patricia TorresMaya-Monteiro, Clarissa M.Melo, Christianne Bandeira2019-01-23T13:21:38Z2019-01-23T13:21:38Z2018AMORIM, Natália R. T. et al. Leptin Elicits LTC4 Synthesis by Eosinophils Mediated by Sequential Two-Step Autocrine Activitation of CCR3 and PGD2 Receptors. Frontiers in Immunology, v.9, Article 2139, 11p, Sept. 2018.1664-3224https://www.arca.fiocruz.br/handle/icict/3124410.3389/fimmu.2018.02139engFrontiers MediaLeptinaProstaglandina D2LeucotrienosGotículas LipídicasLeptinEosonophilProstaglandin D2Leukotriene C4CCR3CCL5Lipid bodyLipid dropletLeptin Elicits LTC4 Synthesis by Eosinophils Mediated by Sequential Two-Step Autocrine Activation of CCR3 and PGD2 Receptorsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Instituto de Aplicação Fernando Rodrigues da Silveira. Departamento de Ciências da Natureza. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.Harvard Medical School. Department of Medicine. Beth Israel Deaconess Medical Center. Boston, MA, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.Leptin is a cytokine, produced mainly by mature adipocytes, that regulates the central nervous system, mainly to suppress appetite and stimulate energy expenditure. Leptin also regulates the immune response by controlling activation of immunomodulatory cells, including eosinophils. While emerging as immune regulatory cells with roles in adipose tissue homeostasis, eosinophils have a well-established ability to synthesize pro-inflammatory molecules such as lipid mediators, a key event in several inflammatory pathologies. Here, we investigated the impact and mechanisms involved in leptin-driven activation of eicosanoid-synthesizing machinery within eosinophils. Direct in vitro activation of human or mouse eosinophils with leptin elicited synthesis of lipoxygenase as well as cyclooxygenase products. Displaying selectivity, leptin triggered synthesis of LTC4 and PGD2, but not PGE2, in parallel to dose-dependent induction of lipid body/lipid droplets biogenesis. While dependent on PI3K activation, leptin-driven eosinophil activation was also sensitive to pertussis toxin, indicating the involvement of G-protein coupled receptors on leptin effects. Leptin-induced lipid body-driven LTC4 synthesis appeared to be mediated through autocrine activation of G-coupled CCR3 receptors by eosinophil-derived CCL5, inasmuch as leptin was able to trigger rapid CCL5 secretion, and neutralizing anti-RANTES or anti-CCR3 antibodies blocked lipid body assembly and LTC4 synthesis induced by leptin. Remarkably, autocrine activation of PGD2 G-coupled receptors DP1 and DP2 also contributes to leptin-elicited lipid body-driven LTC4 synthesis by eosinophils in a PGD2-dependent fashion. Blockade of leptin-induced PGD2 autocrine/paracrine activity by a specific synthesis inhibitor or DP1 and DP2 receptor antagonists, inhibited both lipid body biogenesis and LTC4 synthesis induced by leptin stimulation within eosinophils. In addition, CCL5-driven CCR3 activation appears to precede PGD2 receptor activation within eosinophils, since neutralizing anti-CCL5 or anti-CCR3 antibodies inhibited leptin-induced PGD2 secretion, while it failed to alter PGD2-induced LTC4 synthesis. Altogether, sequential activation of CCR3 and then PGD2 receptors by autocrine ligands in response to leptin stimulation of eosinophils culminates with eosinophil activation, characterized here by assembly of lipidic cytoplasmic platforms synthesis and secretion of the pleiotropic lipid mediators, PGD2, and LTC4.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/31244/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALpatriciabozza_clarissammonteiro_etal_IOC_2018.pdfpatriciabozza_clarissammonteiro_etal_IOC_2018.pdfapplication/pdf1853886https://www.arca.fiocruz.br/bitstream/icict/31244/2/patriciabozza_clarissammonteiro_etal_IOC_2018.pdfe69546af57ccd65b74b9af1a7f945649MD52TEXTpatriciabozza_clarissammonteiro_etal_IOC_2018.pdf.txtpatriciabozza_clarissammonteiro_etal_IOC_2018.pdf.txtExtracted 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| dc.title.pt_BR.fl_str_mv |
Leptin Elicits LTC4 Synthesis by Eosinophils Mediated by Sequential Two-Step Autocrine Activation of CCR3 and PGD2 Receptors |
| title |
Leptin Elicits LTC4 Synthesis by Eosinophils Mediated by Sequential Two-Step Autocrine Activation of CCR3 and PGD2 Receptors |
| spellingShingle |
Leptin Elicits LTC4 Synthesis by Eosinophils Mediated by Sequential Two-Step Autocrine Activation of CCR3 and PGD2 Receptors Amorim, Natália R. T. Leptina Prostaglandina D2 Leucotrienos Gotículas Lipídicas Leptin Eosonophil Prostaglandin D2 Leukotriene C4 CCR3 CCL5 Lipid body Lipid droplet |
| title_short |
Leptin Elicits LTC4 Synthesis by Eosinophils Mediated by Sequential Two-Step Autocrine Activation of CCR3 and PGD2 Receptors |
| title_full |
Leptin Elicits LTC4 Synthesis by Eosinophils Mediated by Sequential Two-Step Autocrine Activation of CCR3 and PGD2 Receptors |
| title_fullStr |
Leptin Elicits LTC4 Synthesis by Eosinophils Mediated by Sequential Two-Step Autocrine Activation of CCR3 and PGD2 Receptors |
| title_full_unstemmed |
Leptin Elicits LTC4 Synthesis by Eosinophils Mediated by Sequential Two-Step Autocrine Activation of CCR3 and PGD2 Receptors |
| title_sort |
Leptin Elicits LTC4 Synthesis by Eosinophils Mediated by Sequential Two-Step Autocrine Activation of CCR3 and PGD2 Receptors |
| author |
Amorim, Natália R. T. |
| author_facet |
Amorim, Natália R. T. Gomes, Tatiana Luna Almeida, Marcos Gama Almeida, Glaucia Souza Canetti, Claudio Diaz, Bruno L. Weller, Peter F. Bozza, Patricia Torres Maya-Monteiro, Clarissa M. Melo, Christianne Bandeira |
| author_role |
author |
| author2 |
Gomes, Tatiana Luna Almeida, Marcos Gama Almeida, Glaucia Souza Canetti, Claudio Diaz, Bruno L. Weller, Peter F. Bozza, Patricia Torres Maya-Monteiro, Clarissa M. Melo, Christianne Bandeira |
| author2_role |
author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Amorim, Natália R. T. Gomes, Tatiana Luna Almeida, Marcos Gama Almeida, Glaucia Souza Canetti, Claudio Diaz, Bruno L. Weller, Peter F. Bozza, Patricia Torres Maya-Monteiro, Clarissa M. Melo, Christianne Bandeira |
| dc.subject.other.pt_BR.fl_str_mv |
Leptina Prostaglandina D2 Leucotrienos Gotículas Lipídicas |
| topic |
Leptina Prostaglandina D2 Leucotrienos Gotículas Lipídicas Leptin Eosonophil Prostaglandin D2 Leukotriene C4 CCR3 CCL5 Lipid body Lipid droplet |
| dc.subject.en.pt_BR.fl_str_mv |
Leptin Eosonophil Prostaglandin D2 Leukotriene C4 CCR3 CCL5 Lipid body Lipid droplet |
| description |
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. |
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2018 |
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2018 |
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2019-01-23T13:21:38Z |
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2019-01-23T13:21:38Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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AMORIM, Natália R. T. et al. Leptin Elicits LTC4 Synthesis by Eosinophils Mediated by Sequential Two-Step Autocrine Activitation of CCR3 and PGD2 Receptors. Frontiers in Immunology, v.9, Article 2139, 11p, Sept. 2018. |
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https://www.arca.fiocruz.br/handle/icict/31244 |
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1664-3224 |
| dc.identifier.eissn.none.fl_str_mv |
10.3389/fimmu.2018.02139 |
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AMORIM, Natália R. T. et al. Leptin Elicits LTC4 Synthesis by Eosinophils Mediated by Sequential Two-Step Autocrine Activitation of CCR3 and PGD2 Receptors. Frontiers in Immunology, v.9, Article 2139, 11p, Sept. 2018. 1664-3224 10.3389/fimmu.2018.02139 |
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Frontiers Media |
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Frontiers Media |
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