PMID- 11849317 OWN - NLM STAT- MEDLINE DCOM- 20020304 LR - 20190513 IS - 0019-2805 (Print) IS - 1365-2567 (Electronic) IS - 0019-2805 (Linking) VI - 105 IP - 1 DP - 2002 Jan TI - Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases define the migratory characteristics of human monocyte-derived dendritic cells. PG - 73-82 AB - Dendritic cells (DCs) have an essential role in the initiation of immune responses as they deliver antigen/epitope and the appropriate signals to activate naive 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-alpha (TNF-alpha) 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. FAU - Osman, Mohamed AU - Osman M AD - Imperial College School of Medicine, Kennedy Institute of Rheumatology Division, London, UK. m.osman@ic.ac.uk FAU - Tortorella, Micky AU - Tortorella M FAU - Londei, Marco AU - Londei M FAU - Quaratino, Sonia AU - Quaratino S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (Tissue Inhibitor of Metalloproteinases) RN - 0 (Tumor Necrosis Factor-alpha) RN - 207137-56-2 (Interleukin-4) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - Blotting, Western MH - Cell Migration Inhibition MH - Cell Movement/*physiology MH - Dendritic Cells/cytology/*physiology MH - Flow Cytometry MH - Granulocyte-Macrophage Colony-Stimulating Factor/physiology MH - Humans MH - Interleukin-4/physiology MH - Matrix Metalloproteinases/*physiology MH - Monocytes/*physiology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tissue Inhibitor of Metalloproteinases/*physiology MH - Tumor Necrosis Factor-alpha/physiology MH - Vaccinia virus/physiology PMC - PMC1782644 EDAT- 2002/02/19 10:00 MHDA- 2002/03/05 10:01 PMCR- 2003/01/01 CRDT- 2002/02/19 10:00 PHST- 2002/02/19 10:00 [pubmed] PHST- 2002/03/05 10:01 [medline] PHST- 2002/02/19 10:00 [entrez] PHST- 2003/01/01 00:00 [pmc-release] AID - 1349 [pii] AID - 10.1046/j.0019-2805.2001.01349.x [doi] PST - ppublish SO - Immunology. 2002 Jan;105(1):73-82. doi: 10.1046/j.0019-2805.2001.01349.x.