Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1177/1753425916684934 http://hdl.handle.net/11449/169599 |
Resumo: | Alveolar macrophages (AMs) are multitasking cells that maintain lung homeostasis by clearing apoptotic cells (efferocytosis) and performing antimicrobial effector functions. Different PRRs have been described to be involved in the binding and capture of non-opsonized Streptococcus pneumoniae, such as TLR-2, mannose receptor (MR) and scavenger receptors (SRs). However, the mechanism by which the ingestion of apoptotic cells negatively influences the clearance of non-opsonized S. pneumoniae remains to be determined. In this study, we evaluated whether the prostaglandin E2 (PGE2) produced during efferocytosis by AMs inhibits the ingestion and killing of non-opsonized S. pneumoniae. Resident AMs were pre-treated with an E prostanoid (EP) receptor antagonist, inhibitors of cyclooxygenase and protein kinase A (PKA), incubated with apoptotic Jurkat T cells, and then challenged with S. pneumoniae. Efferocytosis slightly decreased the phagocytosis of S. pneumoniae but greatly inhibited bacterial killing by AMs in a manner dependent on PGE2 production, activation of the EP2-EP4/cAMP/PKA pathway and inhibition of H2O2 production. Our data suggest that the PGE2 produced by AMs during efferocytosis inhibits H2O2 production and impairs the efficient clearance non-opsonized S. pneumoniae by EP2-EP4/cAMP/PKA pathway. |
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Repositório Institucional da UNESP |
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Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infectionalveolar macrophagesapoptotic cellsEfferocytosisprostaglandin E2Streptococcus pneumoniaeAlveolar macrophages (AMs) are multitasking cells that maintain lung homeostasis by clearing apoptotic cells (efferocytosis) and performing antimicrobial effector functions. Different PRRs have been described to be involved in the binding and capture of non-opsonized Streptococcus pneumoniae, such as TLR-2, mannose receptor (MR) and scavenger receptors (SRs). However, the mechanism by which the ingestion of apoptotic cells negatively influences the clearance of non-opsonized S. pneumoniae remains to be determined. In this study, we evaluated whether the prostaglandin E2 (PGE2) produced during efferocytosis by AMs inhibits the ingestion and killing of non-opsonized S. pneumoniae. Resident AMs were pre-treated with an E prostanoid (EP) receptor antagonist, inhibitors of cyclooxygenase and protein kinase A (PKA), incubated with apoptotic Jurkat T cells, and then challenged with S. pneumoniae. Efferocytosis slightly decreased the phagocytosis of S. pneumoniae but greatly inhibited bacterial killing by AMs in a manner dependent on PGE2 production, activation of the EP2-EP4/cAMP/PKA pathway and inhibition of H2O2 production. Our data suggest that the PGE2 produced by AMs during efferocytosis inhibits H2O2 production and impairs the efficient clearance non-opsonized S. pneumoniae by EP2-EP4/cAMP/PKA pathway.Department of Biological Science School of Pharmaceutical Science São Paulo State University (UNESP), Araraquara/Jau Km 1Department of Medicine Vanderbilt University Medical CenterDepartment of Biological Science School of Pharmaceutical Science São Paulo State University (UNESP), Araraquara/Jau Km 1Universidade Estadual Paulista (Unesp)Vanderbilt University Medical CenterSalina, Ana C.G. [UNESP]Souza, Tais P. [UNESP]Serezani, Carlos H.Medeiros, Alexandra I. [UNESP]2018-12-11T16:46:46Z2018-12-11T16:46:46Z2017-04-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article219-227application/pdfhttp://dx.doi.org/10.1177/1753425916684934Innate Immunity, v. 23, n. 3, p. 219-227, 2017.1753-42671753-4259http://hdl.handle.net/11449/16959910.1177/17534259166849342-s2.0-850167235002-s2.0-85016723500.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInnate Immunity1,0311,031info:eu-repo/semantics/openAccess2024-01-24T06:34:21Zoai:repositorio.unesp.br:11449/169599Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-01-24T06:34:21Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection |
title |
Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection |
spellingShingle |
Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection Salina, Ana C.G. [UNESP] alveolar macrophages apoptotic cells Efferocytosis prostaglandin E2 Streptococcus pneumoniae |
title_short |
Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection |
title_full |
Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection |
title_fullStr |
Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection |
title_full_unstemmed |
Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection |
title_sort |
Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection |
author |
Salina, Ana C.G. [UNESP] |
author_facet |
Salina, Ana C.G. [UNESP] Souza, Tais P. [UNESP] Serezani, Carlos H. Medeiros, Alexandra I. [UNESP] |
author_role |
author |
author2 |
Souza, Tais P. [UNESP] Serezani, Carlos H. Medeiros, Alexandra I. [UNESP] |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Vanderbilt University Medical Center |
dc.contributor.author.fl_str_mv |
Salina, Ana C.G. [UNESP] Souza, Tais P. [UNESP] Serezani, Carlos H. Medeiros, Alexandra I. [UNESP] |
dc.subject.por.fl_str_mv |
alveolar macrophages apoptotic cells Efferocytosis prostaglandin E2 Streptococcus pneumoniae |
topic |
alveolar macrophages apoptotic cells Efferocytosis prostaglandin E2 Streptococcus pneumoniae |
description |
Alveolar macrophages (AMs) are multitasking cells that maintain lung homeostasis by clearing apoptotic cells (efferocytosis) and performing antimicrobial effector functions. Different PRRs have been described to be involved in the binding and capture of non-opsonized Streptococcus pneumoniae, such as TLR-2, mannose receptor (MR) and scavenger receptors (SRs). However, the mechanism by which the ingestion of apoptotic cells negatively influences the clearance of non-opsonized S. pneumoniae remains to be determined. In this study, we evaluated whether the prostaglandin E2 (PGE2) produced during efferocytosis by AMs inhibits the ingestion and killing of non-opsonized S. pneumoniae. Resident AMs were pre-treated with an E prostanoid (EP) receptor antagonist, inhibitors of cyclooxygenase and protein kinase A (PKA), incubated with apoptotic Jurkat T cells, and then challenged with S. pneumoniae. Efferocytosis slightly decreased the phagocytosis of S. pneumoniae but greatly inhibited bacterial killing by AMs in a manner dependent on PGE2 production, activation of the EP2-EP4/cAMP/PKA pathway and inhibition of H2O2 production. Our data suggest that the PGE2 produced by AMs during efferocytosis inhibits H2O2 production and impairs the efficient clearance non-opsonized S. pneumoniae by EP2-EP4/cAMP/PKA pathway. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-04-01 2018-12-11T16:46:46Z 2018-12-11T16:46:46Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1177/1753425916684934 Innate Immunity, v. 23, n. 3, p. 219-227, 2017. 1753-4267 1753-4259 http://hdl.handle.net/11449/169599 10.1177/1753425916684934 2-s2.0-85016723500 2-s2.0-85016723500.pdf |
url |
http://dx.doi.org/10.1177/1753425916684934 http://hdl.handle.net/11449/169599 |
identifier_str_mv |
Innate Immunity, v. 23, n. 3, p. 219-227, 2017. 1753-4267 1753-4259 10.1177/1753425916684934 2-s2.0-85016723500 2-s2.0-85016723500.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Innate Immunity 1,031 1,031 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
219-227 application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1799965715513475072 |