Restoration of the normal Clara cell phenotype after chronic allergic inflammation

Autores
Roth, Félix Daniel; Quintar, Amado Alfredo; Leimgruber, Carolina; García, Luciana; Uribe Echevarría, Elisa M.; Torres, Alicia Ines; Maldonado, Cristina Alicia
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Bronchiolar Clara cells play a critical role in lung homoeostasis. The main goal of this study was to evaluate the effects of chronic allergy on these cells and the efficacy of budesonide (BUD) and montelukast (MK) in restoring their typical phenotypes after ovalbumin-induced chronic allergy in mice. Chronic allergy induced extensive bronchiolar Alcian blue-periodic acid-Schiff (AB/PAS)-positive metaplasia. In addition, cells accumulated numerous big electron-lucent granules negative for Clara cell main secretory protein (CC16), and consequently, CC16 was significantly reduced in bronchoalveolar lavage. A concomitant reduction in SP-D and CYP2E1 content was observed. The phenotypic changes induced by allergy were pharmacologically reversed by both treatments; MK was more efficient than BUD in doing so. MK decreased AB/PAS reactivity to control levels whereas they remained persistently elevated after BUD. Moreover, most non-ciliated cells recovered their normal morphology after MK, whereas for BUD normal cells coexisted with ‘transitional’ cells that contained remnant mucous granules and stained strongly for CC16 and SP-D. Glucocorticoids were also less able to reduce inflammatory infiltration and maintained higher percentage of neutrophils, which may have contributed to prolonged mucin expression. These results show that chronic allergy-induced mucous metaplasia of Clara cells affects their defensive mechanisms. However, anti-inflammatory treatments were able to re-establish the normal phenotype of Clara cell, with MK being more efficient at restoring a normal profile than BUD. This study highlights the role of epithelial cells in lung injuries and their contribution to anti-inflammatory therapies.
Fil: Roth, Félix Daniel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: Quintar, Amado Alfredo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: Leimgruber, Carolina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: García, Luciana. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: Uribe Echevarría, Elisa M.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina. Sanatorio Allende; Argentina
Fil: Torres, Alicia Ines. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: Maldonado, Cristina Alicia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Materia
Clara Cells
Budesoniide
Asthma
Innate Immunity
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/11511
Acceder
id CONICETDig_6421d9c37737e3344f7745992bfdd18d
oai_identifier_str oai:ri.conicet.gov.ar:11336/11511
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Restoration of the normal Clara cell phenotype after chronic allergic inflammationRoth, Félix DanielQuintar, Amado AlfredoLeimgruber, CarolinaGarcía, LucianaUribe Echevarría, Elisa M.Torres, Alicia InesMaldonado, Cristina AliciaClara CellsBudesoniideAsthmaInnate Immunityhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Bronchiolar Clara cells play a critical role in lung homoeostasis. The main goal of this study was to evaluate the effects of chronic allergy on these cells and the efficacy of budesonide (BUD) and montelukast (MK) in restoring their typical phenotypes after ovalbumin-induced chronic allergy in mice. Chronic allergy induced extensive bronchiolar Alcian blue-periodic acid-Schiff (AB/PAS)-positive metaplasia. In addition, cells accumulated numerous big electron-lucent granules negative for Clara cell main secretory protein (CC16), and consequently, CC16 was significantly reduced in bronchoalveolar lavage. A concomitant reduction in SP-D and CYP2E1 content was observed. The phenotypic changes induced by allergy were pharmacologically reversed by both treatments; MK was more efficient than BUD in doing so. MK decreased AB/PAS reactivity to control levels whereas they remained persistently elevated after BUD. Moreover, most non-ciliated cells recovered their normal morphology after MK, whereas for BUD normal cells coexisted with ‘transitional’ cells that contained remnant mucous granules and stained strongly for CC16 and SP-D. Glucocorticoids were also less able to reduce inflammatory infiltration and maintained higher percentage of neutrophils, which may have contributed to prolonged mucin expression. These results show that chronic allergy-induced mucous metaplasia of Clara cells affects their defensive mechanisms. However, anti-inflammatory treatments were able to re-establish the normal phenotype of Clara cell, with MK being more efficient at restoring a normal profile than BUD. This study highlights the role of epithelial cells in lung injuries and their contribution to anti-inflammatory therapies.Fil: Roth, Félix Daniel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; ArgentinaFil: Quintar, Amado Alfredo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; ArgentinaFil: Leimgruber, Carolina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; ArgentinaFil: García, Luciana. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; ArgentinaFil: Uribe Echevarría, Elisa M.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina. Sanatorio Allende; ArgentinaFil: Torres, Alicia Ines. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; ArgentinaFil: Maldonado, Cristina Alicia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; ArgentinaWiley Blackwell Publishing, Inc2013-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/11511Roth, Félix Daniel; Quintar, Amado Alfredo; Leimgruber, Carolina; García, Luciana; Uribe Echevarría, Elisa M.; et al.; Restoration of the normal Clara cell phenotype after chronic allergic inflammation; Wiley Blackwell Publishing, Inc; International Journal Of Experimental Pathology; 94; 6; 12-2013; 399-4110959-96731365-2613enginfo:eu-repo/semantics/altIdentifier/doi/10.1111/iep.12041info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/iep.12041/abstractinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944451/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-04-15T10:15:14Zoai:ri.conicet.gov.ar:11336/11511instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-04-15 10:15:15.099CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Restoration of the normal Clara cell phenotype after chronic allergic inflammation
title Restoration of the normal Clara cell phenotype after chronic allergic inflammation
spellingShingle Restoration of the normal Clara cell phenotype after chronic allergic inflammation
Roth, Félix Daniel
Clara Cells
Budesoniide
Asthma
Innate Immunity
title_short Restoration of the normal Clara cell phenotype after chronic allergic inflammation
title_full Restoration of the normal Clara cell phenotype after chronic allergic inflammation
title_fullStr Restoration of the normal Clara cell phenotype after chronic allergic inflammation
title_full_unstemmed Restoration of the normal Clara cell phenotype after chronic allergic inflammation
title_sort Restoration of the normal Clara cell phenotype after chronic allergic inflammation
dc.creator.none.fl_str_mv Roth, Félix Daniel
Quintar, Amado Alfredo
Leimgruber, Carolina
García, Luciana
Uribe Echevarría, Elisa M.
Torres, Alicia Ines
Maldonado, Cristina Alicia
author Roth, Félix Daniel
author_facet Roth, Félix Daniel
Quintar, Amado Alfredo
Leimgruber, Carolina
García, Luciana
Uribe Echevarría, Elisa M.
Torres, Alicia Ines
Maldonado, Cristina Alicia
author_role author
author2 Quintar, Amado Alfredo
Leimgruber, Carolina
García, Luciana
Uribe Echevarría, Elisa M.
Torres, Alicia Ines
Maldonado, Cristina Alicia
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Clara Cells
Budesoniide
Asthma
Innate Immunity
topic Clara Cells
Budesoniide
Asthma
Innate Immunity
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Bronchiolar Clara cells play a critical role in lung homoeostasis. The main goal of this study was to evaluate the effects of chronic allergy on these cells and the efficacy of budesonide (BUD) and montelukast (MK) in restoring their typical phenotypes after ovalbumin-induced chronic allergy in mice. Chronic allergy induced extensive bronchiolar Alcian blue-periodic acid-Schiff (AB/PAS)-positive metaplasia. In addition, cells accumulated numerous big electron-lucent granules negative for Clara cell main secretory protein (CC16), and consequently, CC16 was significantly reduced in bronchoalveolar lavage. A concomitant reduction in SP-D and CYP2E1 content was observed. The phenotypic changes induced by allergy were pharmacologically reversed by both treatments; MK was more efficient than BUD in doing so. MK decreased AB/PAS reactivity to control levels whereas they remained persistently elevated after BUD. Moreover, most non-ciliated cells recovered their normal morphology after MK, whereas for BUD normal cells coexisted with ‘transitional’ cells that contained remnant mucous granules and stained strongly for CC16 and SP-D. Glucocorticoids were also less able to reduce inflammatory infiltration and maintained higher percentage of neutrophils, which may have contributed to prolonged mucin expression. These results show that chronic allergy-induced mucous metaplasia of Clara cells affects their defensive mechanisms. However, anti-inflammatory treatments were able to re-establish the normal phenotype of Clara cell, with MK being more efficient at restoring a normal profile than BUD. This study highlights the role of epithelial cells in lung injuries and their contribution to anti-inflammatory therapies.
Fil: Roth, Félix Daniel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: Quintar, Amado Alfredo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: Leimgruber, Carolina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: García, Luciana. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: Uribe Echevarría, Elisa M.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina. Sanatorio Allende; Argentina
Fil: Torres, Alicia Ines. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: Maldonado, Cristina Alicia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
description Bronchiolar Clara cells play a critical role in lung homoeostasis. The main goal of this study was to evaluate the effects of chronic allergy on these cells and the efficacy of budesonide (BUD) and montelukast (MK) in restoring their typical phenotypes after ovalbumin-induced chronic allergy in mice. Chronic allergy induced extensive bronchiolar Alcian blue-periodic acid-Schiff (AB/PAS)-positive metaplasia. In addition, cells accumulated numerous big electron-lucent granules negative for Clara cell main secretory protein (CC16), and consequently, CC16 was significantly reduced in bronchoalveolar lavage. A concomitant reduction in SP-D and CYP2E1 content was observed. The phenotypic changes induced by allergy were pharmacologically reversed by both treatments; MK was more efficient than BUD in doing so. MK decreased AB/PAS reactivity to control levels whereas they remained persistently elevated after BUD. Moreover, most non-ciliated cells recovered their normal morphology after MK, whereas for BUD normal cells coexisted with ‘transitional’ cells that contained remnant mucous granules and stained strongly for CC16 and SP-D. Glucocorticoids were also less able to reduce inflammatory infiltration and maintained higher percentage of neutrophils, which may have contributed to prolonged mucin expression. These results show that chronic allergy-induced mucous metaplasia of Clara cells affects their defensive mechanisms. However, anti-inflammatory treatments were able to re-establish the normal phenotype of Clara cell, with MK being more efficient at restoring a normal profile than BUD. This study highlights the role of epithelial cells in lung injuries and their contribution to anti-inflammatory therapies.
publishDate 2013
dc.date.none.fl_str_mv 2013-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/11511
Roth, Félix Daniel; Quintar, Amado Alfredo; Leimgruber, Carolina; García, Luciana; Uribe Echevarría, Elisa M.; et al.; Restoration of the normal Clara cell phenotype after chronic allergic inflammation; Wiley Blackwell Publishing, Inc; International Journal Of Experimental Pathology; 94; 6; 12-2013; 399-411
0959-9673
1365-2613
url http://hdl.handle.net/11336/11511
identifier_str_mv Roth, Félix Daniel; Quintar, Amado Alfredo; Leimgruber, Carolina; García, Luciana; Uribe Echevarría, Elisa M.; et al.; Restoration of the normal Clara cell phenotype after chronic allergic inflammation; Wiley Blackwell Publishing, Inc; International Journal Of Experimental Pathology; 94; 6; 12-2013; 399-411
0959-9673
1365-2613
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/iep.12041
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/iep.12041/abstract
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944451/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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