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Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases define the migratory characteristics of human monocyte-derived dendritic cells

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases define the migratory characteristics of human monocyte-derived dendritic cells
Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases define the migratory characteristics of human monocyte-derived dendritic cells
Dendritic cells (DCs) have an essential role in the initiation of immune responses as they deliver antigen/epitope and the appropriate signals to activate naïve T cells and thus start an immune response. In order to fulfil their function, DCs have to patrol different part of the body, thus migrating through the extracellular matrix to sample the local 'antigenic' environment. In the present study, we have investigated which enzymes might be involved in this process using the Matrigel trans-well migration assay, an in vitro model of extracellular matrix migration. In this assay we analysed the migratory ability of interleukin-4 (IL-4)/granulocyte macrophage–colony-stimulating factor (GM-CSF)-derived immature DCs as well as mature DCs, induced by tumour necrosis factor-? (TNF-?) and modified vaccinia virus Ankara (MVA). The 'mature' DCs showed an increased migration through Matrigel, which was significantly inhibited by inhibitors of matrix metalloproteinases (MMP). We also observed that the dominant MMP involved in this process was MMP-9, and a concomitant decrease of the endogenous tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 was also observed. Collectively these data suggest that the balance between MMP/TIMP determines the net migratory capacity of human DCs. Surprisingly, TIMP-3 was significantly increased in mature DC. Our data thus indicate that MMP and TIMP play a role in the migratory ability of human DCs. Our results also suggest that TIMP-3 expression might represent a new marker of maturation of human DCs.
0019-2805
73-82
Osman, Mohamed
d494bec7-1d4b-4923-9697-d124dc031f8a
Tortorella, Micky
efd12309-a4c8-40bc-9d35-4eb11914bfeb
Londei, Marco
8e3daa14-6b85-45b8-bac9-c93b05483434
Quaratino, Sonia
a17d78fe-6c03-4775-83e3-53f9d511ae70
Osman, Mohamed
d494bec7-1d4b-4923-9697-d124dc031f8a
Tortorella, Micky
efd12309-a4c8-40bc-9d35-4eb11914bfeb
Londei, Marco
8e3daa14-6b85-45b8-bac9-c93b05483434
Quaratino, Sonia
a17d78fe-6c03-4775-83e3-53f9d511ae70

Osman, Mohamed, Tortorella, Micky, Londei, Marco and Quaratino, Sonia (2002) Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases define the migratory characteristics of human monocyte-derived dendritic cells. Immunology, 105 (1), 73-82. (doi:10.1046/j.0019-2805.2001.01349.x).

Record type: Article

Abstract

Dendritic cells (DCs) have an essential role in the initiation of immune responses as they deliver antigen/epitope and the appropriate signals to activate naïve T cells and thus start an immune response. In order to fulfil their function, DCs have to patrol different part of the body, thus migrating through the extracellular matrix to sample the local 'antigenic' environment. In the present study, we have investigated which enzymes might be involved in this process using the Matrigel trans-well migration assay, an in vitro model of extracellular matrix migration. In this assay we analysed the migratory ability of interleukin-4 (IL-4)/granulocyte macrophage–colony-stimulating factor (GM-CSF)-derived immature DCs as well as mature DCs, induced by tumour necrosis factor-? (TNF-?) and modified vaccinia virus Ankara (MVA). The 'mature' DCs showed an increased migration through Matrigel, which was significantly inhibited by inhibitors of matrix metalloproteinases (MMP). We also observed that the dominant MMP involved in this process was MMP-9, and a concomitant decrease of the endogenous tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 was also observed. Collectively these data suggest that the balance between MMP/TIMP determines the net migratory capacity of human DCs. Surprisingly, TIMP-3 was significantly increased in mature DC. Our data thus indicate that MMP and TIMP play a role in the migratory ability of human DCs. Our results also suggest that TIMP-3 expression might represent a new marker of maturation of human DCs.

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Published date: 2002

Identifiers

Local EPrints ID: 26506
URI: http://eprints.soton.ac.uk/id/eprint/26506
ISSN: 0019-2805
PURE UUID: cd958782-989b-466d-b645-3228fd32ac8d

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Date deposited: 21 Apr 2006
Last modified: 15 Jul 2019 19:13

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