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Analysis of Protease Activity in Live Antigen-presenting Cells Shows Regulation of the Phagosomal Proteolytic Contents During Dendritic Cell Activation

Here, we describe a new approach designed to monitor the proteolytic activity of maturing phagosomes in live antigen-presenting cells. We find that an ingested particle sequentially encounters distinct protease activities during phagosomal maturation. Incorporation of active proteases into the phago...

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Autores principales: Lennon-Duménil, Ana-Maria, Bakker, Arnold H., Maehr, René, Fiebiger, Edda, Overkleeft, Herman S., Rosemblatt, Mario, Ploegh, Hidde L., Lagaudrière-Gesbert, Cécile
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196045/
https://www.ncbi.nlm.nih.gov/pubmed/12186844
http://dx.doi.org/10.1084/jem.20020327
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author Lennon-Duménil, Ana-Maria
Bakker, Arnold H.
Maehr, René
Fiebiger, Edda
Overkleeft, Herman S.
Rosemblatt, Mario
Ploegh, Hidde L.
Lagaudrière-Gesbert, Cécile
author_facet Lennon-Duménil, Ana-Maria
Bakker, Arnold H.
Maehr, René
Fiebiger, Edda
Overkleeft, Herman S.
Rosemblatt, Mario
Ploegh, Hidde L.
Lagaudrière-Gesbert, Cécile
author_sort Lennon-Duménil, Ana-Maria
collection PubMed
description Here, we describe a new approach designed to monitor the proteolytic activity of maturing phagosomes in live antigen-presenting cells. We find that an ingested particle sequentially encounters distinct protease activities during phagosomal maturation. Incorporation of active proteases into the phagosome of the macrophage cell line J774 indicates that phagosome maturation involves progressive fusion with early and late endocytic compartments. In contrast, phagosome biogenesis in bone marrow–derived dendritic cells (DCs) and macrophages preferentially involves endocytic compartments enriched in cathepsin S. Kinetics of phagosomal maturation is faster in macrophages than in DCs. Furthermore, the delivery of active proteases to the phagosome is significantly reduced after the activation of DCs with lipopolysaccharide. This observation is in agreement with the notion that DCs prevent the premature destruction of antigenic determinants to optimize T cell activation. Phagosomal maturation is therefore a tightly regulated process that varies according to the type and differentiation stage of the phagocyte.
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spelling pubmed-21960452008-04-11 Analysis of Protease Activity in Live Antigen-presenting Cells Shows Regulation of the Phagosomal Proteolytic Contents During Dendritic Cell Activation Lennon-Duménil, Ana-Maria Bakker, Arnold H. Maehr, René Fiebiger, Edda Overkleeft, Herman S. Rosemblatt, Mario Ploegh, Hidde L. Lagaudrière-Gesbert, Cécile J Exp Med Article Here, we describe a new approach designed to monitor the proteolytic activity of maturing phagosomes in live antigen-presenting cells. We find that an ingested particle sequentially encounters distinct protease activities during phagosomal maturation. Incorporation of active proteases into the phagosome of the macrophage cell line J774 indicates that phagosome maturation involves progressive fusion with early and late endocytic compartments. In contrast, phagosome biogenesis in bone marrow–derived dendritic cells (DCs) and macrophages preferentially involves endocytic compartments enriched in cathepsin S. Kinetics of phagosomal maturation is faster in macrophages than in DCs. Furthermore, the delivery of active proteases to the phagosome is significantly reduced after the activation of DCs with lipopolysaccharide. This observation is in agreement with the notion that DCs prevent the premature destruction of antigenic determinants to optimize T cell activation. Phagosomal maturation is therefore a tightly regulated process that varies according to the type and differentiation stage of the phagocyte. The Rockefeller University Press 2002-08-19 /pmc/articles/PMC2196045/ /pubmed/12186844 http://dx.doi.org/10.1084/jem.20020327 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Lennon-Duménil, Ana-Maria
Bakker, Arnold H.
Maehr, René
Fiebiger, Edda
Overkleeft, Herman S.
Rosemblatt, Mario
Ploegh, Hidde L.
Lagaudrière-Gesbert, Cécile
Analysis of Protease Activity in Live Antigen-presenting Cells Shows Regulation of the Phagosomal Proteolytic Contents During Dendritic Cell Activation
title Analysis of Protease Activity in Live Antigen-presenting Cells Shows Regulation of the Phagosomal Proteolytic Contents During Dendritic Cell Activation
title_full Analysis of Protease Activity in Live Antigen-presenting Cells Shows Regulation of the Phagosomal Proteolytic Contents During Dendritic Cell Activation
title_fullStr Analysis of Protease Activity in Live Antigen-presenting Cells Shows Regulation of the Phagosomal Proteolytic Contents During Dendritic Cell Activation
title_full_unstemmed Analysis of Protease Activity in Live Antigen-presenting Cells Shows Regulation of the Phagosomal Proteolytic Contents During Dendritic Cell Activation
title_short Analysis of Protease Activity in Live Antigen-presenting Cells Shows Regulation of the Phagosomal Proteolytic Contents During Dendritic Cell Activation
title_sort analysis of protease activity in live antigen-presenting cells shows regulation of the phagosomal proteolytic contents during dendritic cell activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196045/
https://www.ncbi.nlm.nih.gov/pubmed/12186844
http://dx.doi.org/10.1084/jem.20020327
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