Glucagon reduces neutrophil migration and increases susceptibility to Spesis diabetic mice
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| 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/48263 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. |
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Insuela, Daniella Bianchi ReisFerrero, Maximiliano RubenAlbuquerque, Cassiano Felippe Gonçalves deChaves, Amanda da SilvaSilva, Adriano Yagho Oliveira daFaria Neto, Hugo Caire CastroSimões, Rafael LoureiroBarja-Fidalgo, Thereza ChristinaSilva, Patricia Machado Rodrigues eMartins, Marco AurélioSilva, Adriana RibeiroCarvalho, Vinicius Frias2021-07-16T17:50:56Z2021-07-16T17:50:56Z2021INSUELA, Daniela Bianchi Reis et al. Glucagon Reduces Neutrophil Migration and Increases Susceptibility to Sepsis in Diabetic Mice. Fronti. Immunol., v. 12, Article 633540, 16 p, July 2021.1664-3224https://www.arca.fiocruz.br/handle/icict/4826310.3389/fimmu.2021.633540engFrontiers MediaDiabetesGlucagonNeutrófilosSepsiscAMPDiabetesGlucagonNeutrophilSepsisGlucagon reduces neutrophil migration and increases susceptibility to Spesis diabetic miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. 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 Estado do Rio de Janeiro. Instituto Biomédico. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.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 / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcantara Gomes. Laboratorio de Farmacoligia Celular e Molecular. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcantara Gomes. Laboratorio de Farmacoligia Celular e Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Sepsis is one of the most common comorbidities observed in diabetic patients, associated with a deficient innate immune response. Recently, we have shown that glucagon possesses anti-inflammatory properties. In this study, we investigated if hyperglucagonemia triggered by diabetes might reduce the migration of neutrophils, increasing sepsis susceptibility. 21 days after diabetes induction by intravenous injection of alloxan, we induced moderate sepsis in Swiss-Webster mice through cecum ligation and puncture (CLP). The glucagon receptor (GcgR) antagonist des-his1-[Glu9]-glucagon amide was injected intraperitoneally 24h and 1h before CLP. We also tested the effect of glucagon on CXCL1/KC-induced neutrophil migration to the peritoneal cavity in mice. Neutrophil chemotaxis in vitro was tested using transwell plates, and the expression of total PKA and phospho-PKA was evaluated by western blot. GcgR antagonist restored neutrophil migration, reduced CFU numbers in the peritoneal cavity and improved survival rate of diabetic mice after CLP procedure, however, the treatment did no alter hyperglycemia, CXCL1/KC plasma levels and blood neutrophilia. In addition, glucagon inhibited CXCL1/KC-induced neutrophil migration to the peritoneal cavity of non-diabetic mice. Glucagon also decreased the chemotaxis of neutrophils triggered by CXCL1/KC, PAF, or fMLP in vitro. The inhibitory action of glucagon occurred in parallel with the reduction of CXCL1/KC-induced actin polymerization in neutrophils in vitro, but not CD11a and CD11b translocation to cell surface. The suppressor effect of glucagon on CXCL1/KC-induced neutrophil chemotaxis in vitro was reversed by pre-treatment with GcgR antagonist and adenylyl cyclase or PKA inhibitors. Glucagon also increased PKA phosphorylation directly in neutrophils in vitro. Furthermore, glucagon impaired zymosanA-induced ROS production by neutrophils in vitro. Human neutrophil chemotaxis and adherence to endothelial cells in vitro were inhibited by glucagon treatment. According to our results, this inhibition was independent of CD11a and CD11b translocation to neutrophil surface or neutrophil release of CXCL8/IL-8. Altogether, our results suggest that glucagon may be involved in the reduction of neutrophil migration and increased susceptibility to sepsis in diabetic mice. This work collaborates with better understanding of the increased susceptibility and worsening of sepsis in diabetics, which can contribute to the development of new effective therapeutic strategies for diabetic septic patients.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/48263/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALHugoCFariaNeto_MarcoAurelioMartins_etal_IOC_2021.pdfHugoCFariaNeto_MarcoAurelioMartins_etal_IOC_2021.pdfapplication/pdf1882133https://www.arca.fiocruz.br/bitstream/icict/48263/2/HugoCFariaNeto_MarcoAurelioMartins_etal_IOC_2021.pdfe0b230bb366c9c4b4ee82e4612b2de79MD52TEXTHugoCFariaNeto_MarcoAurelioMartins_etal_IOC_2021.pdf.txtHugoCFariaNeto_MarcoAurelioMartins_etal_IOC_2021.pdf.txtExtracted 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| dc.title.pt_BR.fl_str_mv |
Glucagon reduces neutrophil migration and increases susceptibility to Spesis diabetic mice |
| title |
Glucagon reduces neutrophil migration and increases susceptibility to Spesis diabetic mice |
| spellingShingle |
Glucagon reduces neutrophil migration and increases susceptibility to Spesis diabetic mice Insuela, Daniella Bianchi Reis Diabetes Glucagon Neutrófilos Sepsis cAMP Diabetes Glucagon Neutrophil Sepsis |
| title_short |
Glucagon reduces neutrophil migration and increases susceptibility to Spesis diabetic mice |
| title_full |
Glucagon reduces neutrophil migration and increases susceptibility to Spesis diabetic mice |
| title_fullStr |
Glucagon reduces neutrophil migration and increases susceptibility to Spesis diabetic mice |
| title_full_unstemmed |
Glucagon reduces neutrophil migration and increases susceptibility to Spesis diabetic mice |
| title_sort |
Glucagon reduces neutrophil migration and increases susceptibility to Spesis diabetic mice |
| author |
Insuela, Daniella Bianchi Reis |
| author_facet |
Insuela, Daniella Bianchi Reis Ferrero, Maximiliano Ruben Albuquerque, Cassiano Felippe Gonçalves de Chaves, Amanda da Silva Silva, Adriano Yagho Oliveira da Faria Neto, Hugo Caire Castro Simões, Rafael Loureiro Barja-Fidalgo, Thereza Christina Silva, Patricia Machado Rodrigues e Martins, Marco Aurélio Silva, Adriana Ribeiro Carvalho, Vinicius Frias |
| author_role |
author |
| author2 |
Ferrero, Maximiliano Ruben Albuquerque, Cassiano Felippe Gonçalves de Chaves, Amanda da Silva Silva, Adriano Yagho Oliveira da Faria Neto, Hugo Caire Castro Simões, Rafael Loureiro Barja-Fidalgo, Thereza Christina Silva, Patricia Machado Rodrigues e Martins, Marco Aurélio Silva, Adriana Ribeiro Carvalho, Vinicius Frias |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Insuela, Daniella Bianchi Reis Ferrero, Maximiliano Ruben Albuquerque, Cassiano Felippe Gonçalves de Chaves, Amanda da Silva Silva, Adriano Yagho Oliveira da Faria Neto, Hugo Caire Castro Simões, Rafael Loureiro Barja-Fidalgo, Thereza Christina Silva, Patricia Machado Rodrigues e Martins, Marco Aurélio Silva, Adriana Ribeiro Carvalho, Vinicius Frias |
| dc.subject.other.pt_BR.fl_str_mv |
Diabetes Glucagon Neutrófilos Sepsis |
| topic |
Diabetes Glucagon Neutrófilos Sepsis cAMP Diabetes Glucagon Neutrophil Sepsis |
| dc.subject.en.pt_BR.fl_str_mv |
cAMP Diabetes Glucagon Neutrophil Sepsis |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. |
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2021 |
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2021-07-16T17:50:56Z |
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2021-07-16T17:50:56Z |
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2021 |
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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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INSUELA, Daniela Bianchi Reis et al. Glucagon Reduces Neutrophil Migration and Increases Susceptibility to Sepsis in Diabetic Mice. Fronti. Immunol., v. 12, Article 633540, 16 p, July 2021. |
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https://www.arca.fiocruz.br/handle/icict/48263 |
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1664-3224 |
| dc.identifier.doi.none.fl_str_mv |
10.3389/fimmu.2021.633540 |
| identifier_str_mv |
INSUELA, Daniela Bianchi Reis et al. Glucagon Reduces Neutrophil Migration and Increases Susceptibility to Sepsis in Diabetic Mice. Fronti. Immunol., v. 12, Article 633540, 16 p, July 2021. 1664-3224 10.3389/fimmu.2021.633540 |
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