Functional and Ultrastructural Analysis of Annexin A1 and Its Receptor in Extravasating Neutrophils during Acute Inflammation
Autor(a) principal: | |
---|---|
Data de Publicação: | 2009 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/31135 http://dx.doi.org/10.2353/ajpath.2009.080342 |
Resumo: | The purpose of this study was twofold: to reveal cellular events associated with the protective role of endogenous annexin A1 (AnxA1) in inflammation and to highlight the potential involvement of members of the formyl peptide receptor (Fpr) family in this process. We found that wild-type, AnxA1-null, and Fpr1-null mice all displayed an intense neutrophil recruitment into the peritoneal cavity as assessed 4 hours after carrageenin injection, and that this recruitment was most pronounced in AnxA1-null mice. in addition, this cell influx could be inhibited by the AnxA1 pharmacophore peptide, Ac2-26, in wild-type, AnxA1-null, and Fpr1-null mice, but was restored when co-treated with the pan-receptor antagonist Boc2. Using the LacZ gene reporter assay, an enhancement of AnxA1 gene promoter activity in extravasated neutrophils was evident in AnxA1-null mice; again this response was reduced after peptide treatment. the lack of functional involvement of Fpr1 prompted us to monitor the structurally related receptor Fpr2. We report, for the first time, the ultrastructural immunocytochemical co-localization of Fpr2 with AnxA1 in neutrophils that migrate into the mesenteric microcirculation and extravasate into the peritoneal fluid. Collectively, these data provide in vivo support to the hypothesis that endogenous AnxA1 is an essential effector of endogenous anti-inflammation and provide an ultrastructural indication that this mediator interacts with Fpr2 in murine neutrophils. We believe that these findings could significantly affect the development of novel therapeutics, which are modeled after the anti-migratory actions of AnxA1. (Am J Pathol 2009, 174:177-183; DOI. 10.2353/ajpath.2009.080342) |
id |
UFSP_77650ca544621597a698ef20459ff0a3 |
---|---|
oai_identifier_str |
oai:repositorio.unifesp.br:11600/31135 |
network_acronym_str |
UFSP |
network_name_str |
Repositório Institucional da UNIFESP |
repository_id_str |
3465 |
spelling |
Gastardelo, Thais Santana [UNIFESP]Damazo, Amilcar Sabino [UNIFESP]Dalli, JesmondFlower, Roderick J.Perretti, MauroOliani, Sonia Maria [UNIFESP]São Paulo State UnivUniversidade Federal de São Paulo (UNIFESP)Queen Mary Univ London2016-01-24T13:52:01Z2016-01-24T13:52:01Z2009-01-01American Journal of Pathology. Bethesda: Amer Soc Investigative Pathology, Inc, v. 174, n. 1, p. 177-183, 2009.0002-9440http://repositorio.unifesp.br/handle/11600/31135http://dx.doi.org/10.2353/ajpath.2009.08034210.2353/ajpath.2009.080342WOS:000262219400018The purpose of this study was twofold: to reveal cellular events associated with the protective role of endogenous annexin A1 (AnxA1) in inflammation and to highlight the potential involvement of members of the formyl peptide receptor (Fpr) family in this process. We found that wild-type, AnxA1-null, and Fpr1-null mice all displayed an intense neutrophil recruitment into the peritoneal cavity as assessed 4 hours after carrageenin injection, and that this recruitment was most pronounced in AnxA1-null mice. in addition, this cell influx could be inhibited by the AnxA1 pharmacophore peptide, Ac2-26, in wild-type, AnxA1-null, and Fpr1-null mice, but was restored when co-treated with the pan-receptor antagonist Boc2. Using the LacZ gene reporter assay, an enhancement of AnxA1 gene promoter activity in extravasated neutrophils was evident in AnxA1-null mice; again this response was reduced after peptide treatment. the lack of functional involvement of Fpr1 prompted us to monitor the structurally related receptor Fpr2. We report, for the first time, the ultrastructural immunocytochemical co-localization of Fpr2 with AnxA1 in neutrophils that migrate into the mesenteric microcirculation and extravasate into the peritoneal fluid. Collectively, these data provide in vivo support to the hypothesis that endogenous AnxA1 is an essential effector of endogenous anti-inflammation and provide an ultrastructural indication that this mediator interacts with Fpr2 in murine neutrophils. We believe that these findings could significantly affect the development of novel therapeutics, which are modeled after the anti-migratory actions of AnxA1. (Am J Pathol 2009, 174:177-183; DOI. 10.2353/ajpath.2009.080342)Fundacao de Amparo 6 Pesquisa do Estado de São PauloConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Wellcome TrustWilliam Harvey Research FoundationSão Paulo State Univ, UNESP, Inst Biociencias Letras & Ciencias Exatas, Dept Biol, BR-15054000 São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Paulista Sch Med EPM, São Paulo, BrazilQueen Mary Univ London, Barts & London Med Sch, William Harvey Res Inst, London, EnglandUniversidade Federal de São Paulo, UNIFESP, Paulista Sch Med EPM, São Paulo, BrazilFundacao de Amparo 6 Pesquisa do Estado de São Paulo: 03/11292-0Fundacao de Amparo 6 Pesquisa do Estado de São Paulo: 04/03124-3CNPq: 307920/2004-6Wellcome Trust: 069234/Z/02/ZWeb of Science177-183engAmer Soc Investigative Pathology, IncAmerican Journal of PathologyFunctional and Ultrastructural Analysis of Annexin A1 and Its Receptor in Extravasating Neutrophils during Acute Inflammationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/311352023-02-15 11:04:56.583metadata only accessoai:repositorio.unifesp.br:11600/31135Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-02-15T14:04:56Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Functional and Ultrastructural Analysis of Annexin A1 and Its Receptor in Extravasating Neutrophils during Acute Inflammation |
title |
Functional and Ultrastructural Analysis of Annexin A1 and Its Receptor in Extravasating Neutrophils during Acute Inflammation |
spellingShingle |
Functional and Ultrastructural Analysis of Annexin A1 and Its Receptor in Extravasating Neutrophils during Acute Inflammation Gastardelo, Thais Santana [UNIFESP] |
title_short |
Functional and Ultrastructural Analysis of Annexin A1 and Its Receptor in Extravasating Neutrophils during Acute Inflammation |
title_full |
Functional and Ultrastructural Analysis of Annexin A1 and Its Receptor in Extravasating Neutrophils during Acute Inflammation |
title_fullStr |
Functional and Ultrastructural Analysis of Annexin A1 and Its Receptor in Extravasating Neutrophils during Acute Inflammation |
title_full_unstemmed |
Functional and Ultrastructural Analysis of Annexin A1 and Its Receptor in Extravasating Neutrophils during Acute Inflammation |
title_sort |
Functional and Ultrastructural Analysis of Annexin A1 and Its Receptor in Extravasating Neutrophils during Acute Inflammation |
author |
Gastardelo, Thais Santana [UNIFESP] |
author_facet |
Gastardelo, Thais Santana [UNIFESP] Damazo, Amilcar Sabino [UNIFESP] Dalli, Jesmond Flower, Roderick J. Perretti, Mauro Oliani, Sonia Maria [UNIFESP] |
author_role |
author |
author2 |
Damazo, Amilcar Sabino [UNIFESP] Dalli, Jesmond Flower, Roderick J. Perretti, Mauro Oliani, Sonia Maria [UNIFESP] |
author2_role |
author author author author author |
dc.contributor.institution.none.fl_str_mv |
São Paulo State Univ Universidade Federal de São Paulo (UNIFESP) Queen Mary Univ London |
dc.contributor.author.fl_str_mv |
Gastardelo, Thais Santana [UNIFESP] Damazo, Amilcar Sabino [UNIFESP] Dalli, Jesmond Flower, Roderick J. Perretti, Mauro Oliani, Sonia Maria [UNIFESP] |
description |
The purpose of this study was twofold: to reveal cellular events associated with the protective role of endogenous annexin A1 (AnxA1) in inflammation and to highlight the potential involvement of members of the formyl peptide receptor (Fpr) family in this process. We found that wild-type, AnxA1-null, and Fpr1-null mice all displayed an intense neutrophil recruitment into the peritoneal cavity as assessed 4 hours after carrageenin injection, and that this recruitment was most pronounced in AnxA1-null mice. in addition, this cell influx could be inhibited by the AnxA1 pharmacophore peptide, Ac2-26, in wild-type, AnxA1-null, and Fpr1-null mice, but was restored when co-treated with the pan-receptor antagonist Boc2. Using the LacZ gene reporter assay, an enhancement of AnxA1 gene promoter activity in extravasated neutrophils was evident in AnxA1-null mice; again this response was reduced after peptide treatment. the lack of functional involvement of Fpr1 prompted us to monitor the structurally related receptor Fpr2. We report, for the first time, the ultrastructural immunocytochemical co-localization of Fpr2 with AnxA1 in neutrophils that migrate into the mesenteric microcirculation and extravasate into the peritoneal fluid. Collectively, these data provide in vivo support to the hypothesis that endogenous AnxA1 is an essential effector of endogenous anti-inflammation and provide an ultrastructural indication that this mediator interacts with Fpr2 in murine neutrophils. We believe that these findings could significantly affect the development of novel therapeutics, which are modeled after the anti-migratory actions of AnxA1. (Am J Pathol 2009, 174:177-183; DOI. 10.2353/ajpath.2009.080342) |
publishDate |
2009 |
dc.date.issued.fl_str_mv |
2009-01-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T13:52:01Z |
dc.date.available.fl_str_mv |
2016-01-24T13:52:01Z |
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.citation.fl_str_mv |
American Journal of Pathology. Bethesda: Amer Soc Investigative Pathology, Inc, v. 174, n. 1, p. 177-183, 2009. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/31135 http://dx.doi.org/10.2353/ajpath.2009.080342 |
dc.identifier.issn.none.fl_str_mv |
0002-9440 |
dc.identifier.doi.none.fl_str_mv |
10.2353/ajpath.2009.080342 |
dc.identifier.wos.none.fl_str_mv |
WOS:000262219400018 |
identifier_str_mv |
American Journal of Pathology. Bethesda: Amer Soc Investigative Pathology, Inc, v. 174, n. 1, p. 177-183, 2009. 0002-9440 10.2353/ajpath.2009.080342 WOS:000262219400018 |
url |
http://repositorio.unifesp.br/handle/11600/31135 http://dx.doi.org/10.2353/ajpath.2009.080342 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
American Journal of Pathology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
177-183 |
dc.publisher.none.fl_str_mv |
Amer Soc Investigative Pathology, Inc |
publisher.none.fl_str_mv |
Amer Soc Investigative Pathology, Inc |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
_version_ |
1802764195781935104 |