Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1126/scitranslmed.aac5608 http://hdl.handle.net/11449/172413 |
Resumo: | Microvesicles (MVs) are emerging as a new mechanism of intercellular communication by transferring cellular lipid and protein components to target cells, yet their function in disease is only now being explored. We found that neutrophilderived MVs were increased in concentration in synovial fluid from rheumatoid arthritis patients compared to paired plasma. Synovial MVs overexpressed the proresolving, anti-inflammatory protein annexin A1 (AnxA1). Mice deficient in TMEM16F, a lipid scramblase required for microvesiculation, exhibited exacerbated cartilage damage when subjected to inflammatory arthritis. To determine the function of MVs in inflammatory arthritis, toward the possibility of MV-based therapeutics, we examined the role of immune cell-derived MVs in rodent models and in human primary chondrocytes. In vitro, exogenous neutrophil-derived AnxA1+ MVs activated anabolic gene expression in chondrocytes, leading to extracellular matrix accumulation and cartilage protection through the reduction in stress-adaptive homeostatic mediators interleukin-8 and prostaglandin E2. In vivo, intra-articular injection of AnxA1+ MV lessened cartilage degradation caused by inflammatory arthritis. Arthritic mice receiving adoptive transfer of whole neutrophils displayed abundant MVs within cartilage matrix and revealed that MVs, but not neutrophils themselves, can penetrate cartilage. Mechanistic studies support a model whereby MV-associated AnxA1 interacts with its receptor FPR2 (formyl peptide receptor 2)/ALX, increasing transforming growth factor-p production by chondrocytes, ultimately leading to cartilage protection. We envisage that MVs, either directly or loaded with therapeutics, can be harnessed as a unique therapeutic strategy for protection in diseases associated with cartilage degeneration. |
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spelling |
Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritisMicrovesicles (MVs) are emerging as a new mechanism of intercellular communication by transferring cellular lipid and protein components to target cells, yet their function in disease is only now being explored. We found that neutrophilderived MVs were increased in concentration in synovial fluid from rheumatoid arthritis patients compared to paired plasma. Synovial MVs overexpressed the proresolving, anti-inflammatory protein annexin A1 (AnxA1). Mice deficient in TMEM16F, a lipid scramblase required for microvesiculation, exhibited exacerbated cartilage damage when subjected to inflammatory arthritis. To determine the function of MVs in inflammatory arthritis, toward the possibility of MV-based therapeutics, we examined the role of immune cell-derived MVs in rodent models and in human primary chondrocytes. In vitro, exogenous neutrophil-derived AnxA1+ MVs activated anabolic gene expression in chondrocytes, leading to extracellular matrix accumulation and cartilage protection through the reduction in stress-adaptive homeostatic mediators interleukin-8 and prostaglandin E2. In vivo, intra-articular injection of AnxA1+ MV lessened cartilage degradation caused by inflammatory arthritis. Arthritic mice receiving adoptive transfer of whole neutrophils displayed abundant MVs within cartilage matrix and revealed that MVs, but not neutrophils themselves, can penetrate cartilage. Mechanistic studies support a model whereby MV-associated AnxA1 interacts with its receptor FPR2 (formyl peptide receptor 2)/ALX, increasing transforming growth factor-p production by chondrocytes, ultimately leading to cartilage protection. We envisage that MVs, either directly or loaded with therapeutics, can be harnessed as a unique therapeutic strategy for protection in diseases associated with cartilage degeneration.William Harvey Research Institute Barts and The London School of Medicine Queen Mary University of London, Charterhouse SquareDepartment of Physiology Howard Hughes Medical Institute University of California San FranciscoDepartment of Biology Instituto de Biociências Letras e Ciências Exatas São Paulo State University (UNESP)Department of Rheumatology Barts Health Trust, Bancroft RoadDepartment of Biology Instituto de Biociências Letras e Ciências Exatas São Paulo State University (UNESP)Queen Mary University of LondonSan FranciscoUniversidade Estadual Paulista (Unesp)Barts Health TrustHeadland, Sarah E.Jones, Hefin R.Norling, Lucy V.Kim, AndrewSouza, Patricia R.Corsiero, ElisaGil, Cristiane D. [UNESP]Nerviani, AlessandraDell'accio, FrancescoPitzalis, CostantinoOliani, Sonia M. [UNESP]Jan, Lily Y.Perretti, Mauro2018-12-11T17:00:10Z2018-12-11T17:00:10Z2015-11-25info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1126/scitranslmed.aac5608Science Translational Medicine, v. 7, n. 315, 2015.1946-62421946-6234http://hdl.handle.net/11449/17241310.1126/scitranslmed.aac56082-s2.0-849541970242-s2.0-84954197024.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengScience Translational Medicine9,7009,700info:eu-repo/semantics/openAccess2023-12-25T06:20:30Zoai:repositorio.unesp.br:11449/172413Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:15:29.464206Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis |
title |
Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis |
spellingShingle |
Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis Headland, Sarah E. |
title_short |
Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis |
title_full |
Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis |
title_fullStr |
Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis |
title_full_unstemmed |
Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis |
title_sort |
Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis |
author |
Headland, Sarah E. |
author_facet |
Headland, Sarah E. Jones, Hefin R. Norling, Lucy V. Kim, Andrew Souza, Patricia R. Corsiero, Elisa Gil, Cristiane D. [UNESP] Nerviani, Alessandra Dell'accio, Francesco Pitzalis, Costantino Oliani, Sonia M. [UNESP] Jan, Lily Y. Perretti, Mauro |
author_role |
author |
author2 |
Jones, Hefin R. Norling, Lucy V. Kim, Andrew Souza, Patricia R. Corsiero, Elisa Gil, Cristiane D. [UNESP] Nerviani, Alessandra Dell'accio, Francesco Pitzalis, Costantino Oliani, Sonia M. [UNESP] Jan, Lily Y. Perretti, Mauro |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Queen Mary University of London San Francisco Universidade Estadual Paulista (Unesp) Barts Health Trust |
dc.contributor.author.fl_str_mv |
Headland, Sarah E. Jones, Hefin R. Norling, Lucy V. Kim, Andrew Souza, Patricia R. Corsiero, Elisa Gil, Cristiane D. [UNESP] Nerviani, Alessandra Dell'accio, Francesco Pitzalis, Costantino Oliani, Sonia M. [UNESP] Jan, Lily Y. Perretti, Mauro |
description |
Microvesicles (MVs) are emerging as a new mechanism of intercellular communication by transferring cellular lipid and protein components to target cells, yet their function in disease is only now being explored. We found that neutrophilderived MVs were increased in concentration in synovial fluid from rheumatoid arthritis patients compared to paired plasma. Synovial MVs overexpressed the proresolving, anti-inflammatory protein annexin A1 (AnxA1). Mice deficient in TMEM16F, a lipid scramblase required for microvesiculation, exhibited exacerbated cartilage damage when subjected to inflammatory arthritis. To determine the function of MVs in inflammatory arthritis, toward the possibility of MV-based therapeutics, we examined the role of immune cell-derived MVs in rodent models and in human primary chondrocytes. In vitro, exogenous neutrophil-derived AnxA1+ MVs activated anabolic gene expression in chondrocytes, leading to extracellular matrix accumulation and cartilage protection through the reduction in stress-adaptive homeostatic mediators interleukin-8 and prostaglandin E2. In vivo, intra-articular injection of AnxA1+ MV lessened cartilage degradation caused by inflammatory arthritis. Arthritic mice receiving adoptive transfer of whole neutrophils displayed abundant MVs within cartilage matrix and revealed that MVs, but not neutrophils themselves, can penetrate cartilage. Mechanistic studies support a model whereby MV-associated AnxA1 interacts with its receptor FPR2 (formyl peptide receptor 2)/ALX, increasing transforming growth factor-p production by chondrocytes, ultimately leading to cartilage protection. We envisage that MVs, either directly or loaded with therapeutics, can be harnessed as a unique therapeutic strategy for protection in diseases associated with cartilage degeneration. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-11-25 2018-12-11T17:00:10Z 2018-12-11T17:00:10Z |
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/10.1126/scitranslmed.aac5608 Science Translational Medicine, v. 7, n. 315, 2015. 1946-6242 1946-6234 http://hdl.handle.net/11449/172413 10.1126/scitranslmed.aac5608 2-s2.0-84954197024 2-s2.0-84954197024.pdf |
url |
http://dx.doi.org/10.1126/scitranslmed.aac5608 http://hdl.handle.net/11449/172413 |
identifier_str_mv |
Science Translational Medicine, v. 7, n. 315, 2015. 1946-6242 1946-6234 10.1126/scitranslmed.aac5608 2-s2.0-84954197024 2-s2.0-84954197024.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Science Translational Medicine 9,700 9,700 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
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 |
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1808129301739995136 |