title: Relationship between expression of matrix metalloproteinases and migration of epidermal and in vitro generated Langerhans cells.
abstract: Langerhans cells (LC) are dendritic cells that capture foreign antigens and migrate with them to the regional lymph nodes where they are presented to naive T cells. The possible role of matrix metalloproteinase-9 (MMP-9) in migration was suggested following experiments in a mouse model and in human skin explants. Using in vitro generated LC (iLC) derived from CD34+ cord blood cells and epidermal LC (eLC), we investigated the correlation between MMP-9 and other MMPs production and cell migration. Cells were activated by Bandrowski's base (BB), a chemical allergen, or by recombinant birch pollen allergen 1 (rBetv 1). Contact with allergens triggered migration of these cells, with a maximum rate being reached after 24 h. Migration was preceded by production of MMP-2 and MMP-9; part of the molecules were recovered as pro-MMPs in cell culture supernatant and part were associated with cell membrane proteins. At the cellular level, membrane-type 1 (MT1) and MT3-MMP were also identified. Addition of tumor necrosis factor-alpha (TNF-alpha) initiated pro-MMP-2 and pro-MMP-9 production followed by cell migration in a dose-dependent manner. These data imply that TNF-alpha is a key molecule for MMP production and cell migration. Furthermore, activation of iLC with BB or rBet v 1 induced synthesis of TNF-a and expression of TNF RII on the cell membrane, suggesting an autocrine loop. In conclusion, membrane-associated MMP-2 and-9 rather than soluble MMPs appear to be involved in cell migration.
authors.affiliation: INSERM Unité 346, Laboratoire de Recherche Peau Humaine et Immunité, Hĵpital Edouard Herriot, Lyon, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Noirey
authors.forename: Marie-Jeanne
authors.initials: MJ
authors.lastname: Staquet
authors.forename: Marie-Jo
authors.initials: MJ
authors.lastname: Gariazzo
authors.forename: Mireille
authors.initials: M
authors.lastname: Serres
authors.forename: Claude
authors.initials: C
authors.lastname: André
authors.forename: Daniel
authors.initials: D
authors.lastname: Schmitt
authors.forename: Claude
authors.initials: C
authors.lastname: Vincent
mesh_terms: D000485:Allergens / Q000494:pharmacology; D018952:Antigens, CD34 / Q000378:metabolism; D052179:Antigens, Plant; D001485:Basement Membrane / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D007801:Langerhans Cells / Q000166:cytology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000502:physiology*; D000090023:Metallothionein 3; D010641:Phenotype; D010655:Phenylenediamines / Q000494:pharmacology; D010940:Plant Proteins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000485:Allergens; D018952:Antigens, CD34; D052179:Antigens, Plant; D000090023:Metallothionein 3; C000715430:Mt3 protein, mouse; D010655:Phenylenediamines; D010940:Plant Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C061312:Bet v 1 allergen, Betula; C051597:Bandrowski's base; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9