Neutrophil elastase converts human immature dendritic cells into transforming growth factor-β1-secreting cells and reduces allostimulatory ability

Autores
Maffia, Paulo Cesar; Zittermann, Sandra Elizabeth; Scimone, María Lucila; Tateosian, Nancy Liliana; Amiano, Nicolás Oscar; Guerrieri, Diego; Lutzky, Viviana; Rosso, Diego; Romeo, Horacio Eduardo; García, Verónica Edith; Issekutz, Andrew C.; Chuluyan, Hector Eduardo
Año de publicación
2007
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
During microbial infection, neutrophils (polymorphonuclear leukocytes; PMNs) activate dendritic cells (DCs). However, early reports illustrated that neutrophil-derived mediators may suppress responses to mitogens. In the present study, we investigated the mechanism used by PMNs to modulate the immunostimulatory ability of DCs. Autologous syngeneic PMNs decreased T-cell proliferation induced by allogeneic DCs. Culture supernatant (CS) derived from PMNs also decreased allostimulation ability of immature DCs and increased the expression of transforming growth factor (TGF)-β1 on DCs. A TGF-β1 monoclonal antibody, a CD40 monoclonal antibody, or a serine protease inhibitor reversed the effect of PMN CS on DC allostimulatory ability. Furthermore, elastase reproduced the inhibitory effect of PMN CS on DC allostimulatory ability and the TGF-β1 production. The role of elastase was confirmed by examining PMN CS from two patients with cyclic neutropenia, a disease due to mutations in the neutrophil elastase gene. These PMN CS samples had reduced elastase activity and were unable to increase DC TGF-β1 production. Moreover, elastase and PMN CS induced IκBα; degradation in DCs. We conclude that PMNs decrease DC allostimulatory ability via production of elastase leading to a switch of immature DCs into TGF-β1-secreting cells.
Fil: Maffia, Paulo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Zittermann, Sandra Elizabeth. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Scimone, María Lucila. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Tateosian, Nancy Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Amiano, Nicolás Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Guerrieri, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Lutzky, Viviana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Rosso, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Romeo, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of California at Los Angeles; Estados Unidos
Fil: García, Verónica Edith. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Issekutz, Andrew C.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Chuluyan, Hector Eduardo. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
DENDRITIC CELLS
TTGF
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:11336/99360
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Neutrophil elastase converts human immature dendritic cells into transforming growth factor-β1-secreting cells and reduces allostimulatory abilityMaffia, Paulo CesarZittermann, Sandra ElizabethScimone, María LucilaTateosian, Nancy LilianaAmiano, Nicolás OscarGuerrieri, DiegoLutzky, VivianaRosso, DiegoRomeo, Horacio EduardoGarcía, Verónica EdithIssekutz, Andrew C.Chuluyan, Hector EduardoDENDRITIC CELLSTTGFhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1During microbial infection, neutrophils (polymorphonuclear leukocytes; PMNs) activate dendritic cells (DCs). However, early reports illustrated that neutrophil-derived mediators may suppress responses to mitogens. In the present study, we investigated the mechanism used by PMNs to modulate the immunostimulatory ability of DCs. Autologous syngeneic PMNs decreased T-cell proliferation induced by allogeneic DCs. Culture supernatant (CS) derived from PMNs also decreased allostimulation ability of immature DCs and increased the expression of transforming growth factor (TGF)-β1 on DCs. A TGF-β1 monoclonal antibody, a CD40 monoclonal antibody, or a serine protease inhibitor reversed the effect of PMN CS on DC allostimulatory ability. Furthermore, elastase reproduced the inhibitory effect of PMN CS on DC allostimulatory ability and the TGF-β1 production. The role of elastase was confirmed by examining PMN CS from two patients with cyclic neutropenia, a disease due to mutations in the neutrophil elastase gene. These PMN CS samples had reduced elastase activity and were unable to increase DC TGF-β1 production. Moreover, elastase and PMN CS induced IκBα; degradation in DCs. We conclude that PMNs decrease DC allostimulatory ability via production of elastase leading to a switch of immature DCs into TGF-β1-secreting cells.Fil: Maffia, Paulo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Zittermann, Sandra Elizabeth. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Scimone, María Lucila. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Tateosian, Nancy Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Amiano, Nicolás Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Guerrieri, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Lutzky, Viviana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Rosso, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Romeo, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of California at Los Angeles; Estados UnidosFil: García, Verónica Edith. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Issekutz, Andrew C.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Chuluyan, Hector Eduardo. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAmerican Society of Investigative Pathology2007-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/99360Maffia, Paulo Cesar; Zittermann, Sandra Elizabeth; Scimone, María Lucila; Tateosian, Nancy Liliana; Amiano, Nicolás Oscar; et al.; Neutrophil elastase converts human immature dendritic cells into transforming growth factor-β1-secreting cells and reduces allostimulatory ability; American Society of Investigative Pathology; American Journal Of Pathology; 171; 3; 12-2007; 928-9370002-9440CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S000294401062024Xinfo:eu-repo/semantics/altIdentifier/doi/10.2353/ajpath.2007.061043info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:09:24Zoai:ri.conicet.gov.ar:11336/99360instacron: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:34982025-09-10 13:09:24.356CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Neutrophil elastase converts human immature dendritic cells into transforming growth factor-β1-secreting cells and reduces allostimulatory ability
title Neutrophil elastase converts human immature dendritic cells into transforming growth factor-β1-secreting cells and reduces allostimulatory ability
spellingShingle Neutrophil elastase converts human immature dendritic cells into transforming growth factor-β1-secreting cells and reduces allostimulatory ability
Maffia, Paulo Cesar
DENDRITIC CELLS
TTGF
title_short Neutrophil elastase converts human immature dendritic cells into transforming growth factor-β1-secreting cells and reduces allostimulatory ability
title_full Neutrophil elastase converts human immature dendritic cells into transforming growth factor-β1-secreting cells and reduces allostimulatory ability
title_fullStr Neutrophil elastase converts human immature dendritic cells into transforming growth factor-β1-secreting cells and reduces allostimulatory ability
title_full_unstemmed Neutrophil elastase converts human immature dendritic cells into transforming growth factor-β1-secreting cells and reduces allostimulatory ability
title_sort Neutrophil elastase converts human immature dendritic cells into transforming growth factor-β1-secreting cells and reduces allostimulatory ability
dc.creator.none.fl_str_mv Maffia, Paulo Cesar
Zittermann, Sandra Elizabeth
Scimone, María Lucila
Tateosian, Nancy Liliana
Amiano, Nicolás Oscar
Guerrieri, Diego
Lutzky, Viviana
Rosso, Diego
Romeo, Horacio Eduardo
García, Verónica Edith
Issekutz, Andrew C.
Chuluyan, Hector Eduardo
author Maffia, Paulo Cesar
author_facet Maffia, Paulo Cesar
Zittermann, Sandra Elizabeth
Scimone, María Lucila
Tateosian, Nancy Liliana
Amiano, Nicolás Oscar
Guerrieri, Diego
Lutzky, Viviana
Rosso, Diego
Romeo, Horacio Eduardo
García, Verónica Edith
Issekutz, Andrew C.
Chuluyan, Hector Eduardo
author_role author
author2 Zittermann, Sandra Elizabeth
Scimone, María Lucila
Tateosian, Nancy Liliana
Amiano, Nicolás Oscar
Guerrieri, Diego
Lutzky, Viviana
Rosso, Diego
Romeo, Horacio Eduardo
García, Verónica Edith
Issekutz, Andrew C.
Chuluyan, Hector Eduardo
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DENDRITIC CELLS
TTGF
topic DENDRITIC CELLS
TTGF
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv During microbial infection, neutrophils (polymorphonuclear leukocytes; PMNs) activate dendritic cells (DCs). However, early reports illustrated that neutrophil-derived mediators may suppress responses to mitogens. In the present study, we investigated the mechanism used by PMNs to modulate the immunostimulatory ability of DCs. Autologous syngeneic PMNs decreased T-cell proliferation induced by allogeneic DCs. Culture supernatant (CS) derived from PMNs also decreased allostimulation ability of immature DCs and increased the expression of transforming growth factor (TGF)-β1 on DCs. A TGF-β1 monoclonal antibody, a CD40 monoclonal antibody, or a serine protease inhibitor reversed the effect of PMN CS on DC allostimulatory ability. Furthermore, elastase reproduced the inhibitory effect of PMN CS on DC allostimulatory ability and the TGF-β1 production. The role of elastase was confirmed by examining PMN CS from two patients with cyclic neutropenia, a disease due to mutations in the neutrophil elastase gene. These PMN CS samples had reduced elastase activity and were unable to increase DC TGF-β1 production. Moreover, elastase and PMN CS induced IκBα; degradation in DCs. We conclude that PMNs decrease DC allostimulatory ability via production of elastase leading to a switch of immature DCs into TGF-β1-secreting cells.
Fil: Maffia, Paulo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Zittermann, Sandra Elizabeth. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Scimone, María Lucila. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Tateosian, Nancy Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Amiano, Nicolás Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Guerrieri, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Lutzky, Viviana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Rosso, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Romeo, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of California at Los Angeles; Estados Unidos
Fil: García, Verónica Edith. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Issekutz, Andrew C.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Chuluyan, Hector Eduardo. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description During microbial infection, neutrophils (polymorphonuclear leukocytes; PMNs) activate dendritic cells (DCs). However, early reports illustrated that neutrophil-derived mediators may suppress responses to mitogens. In the present study, we investigated the mechanism used by PMNs to modulate the immunostimulatory ability of DCs. Autologous syngeneic PMNs decreased T-cell proliferation induced by allogeneic DCs. Culture supernatant (CS) derived from PMNs also decreased allostimulation ability of immature DCs and increased the expression of transforming growth factor (TGF)-β1 on DCs. A TGF-β1 monoclonal antibody, a CD40 monoclonal antibody, or a serine protease inhibitor reversed the effect of PMN CS on DC allostimulatory ability. Furthermore, elastase reproduced the inhibitory effect of PMN CS on DC allostimulatory ability and the TGF-β1 production. The role of elastase was confirmed by examining PMN CS from two patients with cyclic neutropenia, a disease due to mutations in the neutrophil elastase gene. These PMN CS samples had reduced elastase activity and were unable to increase DC TGF-β1 production. Moreover, elastase and PMN CS induced IκBα; degradation in DCs. We conclude that PMNs decrease DC allostimulatory ability via production of elastase leading to a switch of immature DCs into TGF-β1-secreting cells.
publishDate 2007
dc.date.none.fl_str_mv 2007-12
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/11336/99360
Maffia, Paulo Cesar; Zittermann, Sandra Elizabeth; Scimone, María Lucila; Tateosian, Nancy Liliana; Amiano, Nicolás Oscar; et al.; Neutrophil elastase converts human immature dendritic cells into transforming growth factor-β1-secreting cells and reduces allostimulatory ability; American Society of Investigative Pathology; American Journal Of Pathology; 171; 3; 12-2007; 928-937
0002-9440
CONICET Digital
CONICET
url http://hdl.handle.net/11336/99360
identifier_str_mv Maffia, Paulo Cesar; Zittermann, Sandra Elizabeth; Scimone, María Lucila; Tateosian, Nancy Liliana; Amiano, Nicolás Oscar; et al.; Neutrophil elastase converts human immature dendritic cells into transforming growth factor-β1-secreting cells and reduces allostimulatory ability; American Society of Investigative Pathology; American Journal Of Pathology; 171; 3; 12-2007; 928-937
0002-9440
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S000294401062024X
info:eu-repo/semantics/altIdentifier/doi/10.2353/ajpath.2007.061043
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
dc.publisher.none.fl_str_mv American Society of Investigative Pathology
publisher.none.fl_str_mv American Society of Investigative Pathology
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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score 12.993085

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