Document Detail

Matrix metalloproteinases 9 and 2 are necessary for the migration of Langerhans cells and dermal dendritic cells from human and murine skin.
MedLine Citation:
PMID:  11970978     Owner:  NLM     Status:  MEDLINE    
Dendritic cells migrate from the skin to the draining lymph nodes. They transport immunogenic MHC-peptide complexes, present them to Ag-specific T cells in the T areas, and thus generate immunity. Migrating dendritic cells encounter physical obstacles, such as basement membranes and collagen meshwork. Prior work has revealed that matrix metalloproteinase-9 (MMP-9) contributes to mouse Langerhans cell migration. In this study, we use mouse and human skin explant culture models to further study the role of MMPs in the migration and maturation of skin dendritic cells. We found that MMP-2 and MMP-9 are expressed on the surface of dendritic cells from the skin, but not from other sources. They are also expressed in migrating Langerhans cells in situ. The migration of both Langerhans cells and dermal dendritic cells is inhibited by a broad spectrum inhibitor of MMPs (BB-3103), by Abs to MMP-9 and -2, and by the natural tissue inhibitors of metalloproteinases (TIMP), TIMP-1 and TIMP-2. Inhibition by anti-MMP-2 and TIMP-2 define a functional role for MMP-2 in addition to the previously described function of MMP-9. The importance of MMP-9 was emphasized using MMP-9-deficient mice in which Langerhans cell migration from skin explants was strikingly reduced. However, MMP-9 was only required for Langerhans cell migration and not maturation, since nonmigrating Langerhans cells isolated from the epidermis matured normally with regard to morphology, phenotype, and T cell stimulatory function. These data underscore the importance of MMPs, and they may be of relevance for therapeutically regulating dendritic cell migration in clinical vaccination approaches.
Gudrun Ratzinger; Patrizia Stoitzner; Susanne Ebner; Manfred B Lutz; Guy T Layton; Christian Rainer; Robert M Senior; J Michael Shipley; Peter Fritsch; Gerold Schuler; Nikolaus Romani
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  168     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-04-23     Completed Date:  2002-05-17     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4361-71     Citation Subset:  AIM; IM    
Department of Dermatology, University of Innsbruck, Innsbruck, Austria.
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MeSH Terms
Basement Membrane / physiology
Cell Differentiation
Cell Movement*
Cells, Cultured
Dendritic Cells / immunology*
Dermis / cytology,  immunology
Dose-Response Relationship, Drug
Epidermis / cytology,  immunology
Langerhans Cells / immunology*
Matrix Metalloproteinase 2 / antagonists & inhibitors,  physiology
Matrix Metalloproteinase 9 / antagonists & inhibitors,  genetics,  physiology
Matrix Metalloproteinases / physiology*
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Organ Culture Techniques
Protease Inhibitors / pharmacology
Skin / drug effects,  enzymology,  immunology*
Grant Support
Reg. No./Substance:
0/Protease Inhibitors; EC 3.4.24.-/Matrix Metalloproteinases; EC Metalloproteinase 2; EC Metalloproteinase 9

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