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.
Skip Nav Destination
Article navigation
19 August 2002
Article|
August 19 2002
Analysis of Protease Activity in Live Antigen-presenting Cells Shows Regulation of the Phagosomal Proteolytic Contents During Dendritic Cell Activation
Ana-Maria Lennon-Duménil,
Ana-Maria Lennon-Duménil
1Department of Pathology, Harvard Medical School, Boston, MA 02115
Search for other works by this author on:
Arnold H. Bakker,
Arnold H. Bakker
1Department of Pathology, Harvard Medical School, Boston, MA 02115
Search for other works by this author on:
René Maehr,
René Maehr
1Department of Pathology, Harvard Medical School, Boston, MA 02115
Search for other works by this author on:
Edda Fiebiger,
Edda Fiebiger
1Department of Pathology, Harvard Medical School, Boston, MA 02115
Search for other works by this author on:
Herman S. Overkleeft,
Herman S. Overkleeft
1Department of Pathology, Harvard Medical School, Boston, MA 02115
Search for other works by this author on:
Mario Rosemblatt,
Mario Rosemblatt
2Departamento de Biologia, Facultad de Ciencias, Universidad de Chile, 6842301 Santiago, Chile
Search for other works by this author on:
Hidde L. Ploegh,
Hidde L. Ploegh
1Department of Pathology, Harvard Medical School, Boston, MA 02115
Search for other works by this author on:
Cécile Lagaudrière-Gesbert
Cécile Lagaudrière-Gesbert
1Department of Pathology, Harvard Medical School, Boston, MA 02115
Search for other works by this author on:
Ana-Maria Lennon-Duménil
1Department of Pathology, Harvard Medical School, Boston, MA 02115
Arnold H. Bakker
1Department of Pathology, Harvard Medical School, Boston, MA 02115
René Maehr
1Department of Pathology, Harvard Medical School, Boston, MA 02115
Edda Fiebiger
1Department of Pathology, Harvard Medical School, Boston, MA 02115
Herman S. Overkleeft
1Department of Pathology, Harvard Medical School, Boston, MA 02115
Mario Rosemblatt
2Departamento de Biologia, Facultad de Ciencias, Universidad de Chile, 6842301 Santiago, Chile
Hidde L. Ploegh
1Department of Pathology, Harvard Medical School, Boston, MA 02115
Cécile Lagaudrière-Gesbert
1Department of Pathology, Harvard Medical School, Boston, MA 02115
Address correspondence to Hidde L. Ploegh, Department of Pathology, 200 Longwood Avenue, Building 2, Room 137, Boston, MA 02115. Phone: 617-432-4777; Fax: 617-432-4775; E-mail: [email protected]
A.M. Lennon-Duménil and A.H. Bakker contributed equally to this work.
*
Abbreviations used in this paper: Cat, cathepsin; ConB, concanamycin B; DC, dendritic cell; MACS, magnetic-activated cell sorting.
Received:
February 27 2002
Revision Received:
June 28 2002
Accepted:
July 17 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2002
J Exp Med (2002) 196 (4): 529–540.
Article history
Received:
February 27 2002
Revision Received:
June 28 2002
Accepted:
July 17 2002
Citation
Ana-Maria Lennon-Duménil, Arnold H. Bakker, René Maehr, Edda Fiebiger, Herman S. Overkleeft, Mario Rosemblatt, Hidde L. Ploegh, Cécile Lagaudrière-Gesbert; Analysis of Protease Activity in Live Antigen-presenting Cells Shows Regulation of the Phagosomal Proteolytic Contents During Dendritic Cell Activation . J Exp Med 19 August 2002; 196 (4): 529–540. doi: https://doi.org/10.1084/jem.20020327
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement