title: Inhibition of contact sensitizer-induced migration of human Langerhans cells by matrix metalloproteinase inhibitors.
abstract: Emigration of Langerhans cells (LC) from the epidermis upon exposure to contact sensitizers is regarded as an essential event in the development of contact sensitization. Since migration of several types of cells depends on the activity of matrix metalloproteinases (MMPs), in the present study we tested whether MMP inhibitors (BB94, BB2116 and CT1166) can prevent the emigration of LC in cultured skin explants, which were exposed to a contact sensitizer (NiSO4). Epicutaneous application of NiSO4 significantly reduced the number of LC within the epidermis and the remaining LC were localized along the epidermal-dermal junction indicating the emigration of LC. In the presence of each of the MMP inhibitors tested, NiSO4-induced migration of LC was strongly decreased. Since after the epicutaneous application of contact sensitizer, its presentation by skin LC is essential for the development of contact sensitization instead of the development of antigen-specific tolerance, our results suggest that the use of MMP inhibitors may be beneficial for the prevention of contact sensitization of the host.
authors.affiliation: Department of Cell Biology and Histology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Lebre
authors.forename: P
authors.initials: P
authors.lastname: Kalinski
authors.forename: P K
authors.initials: PK
authors.lastname: Das
authors.forename: V
authors.initials: V
authors.lastname: Everts
mesh_terms: D000577:Amides / Q000494:pharmacology; D018949:Antigens, CD1 / Q000032:analysis; D002465:Cell Movement / Q000187:drug effects; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects; D006241:Haptens / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007801:Langerhans Cells / Q000187:drug effects* / Q000276:immunology / Q000502:physiology*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D009025:Morpholines / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology*; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D012867:Skin / Q000166:cytology / Q000187:drug effects; D013876:Thiophenes / Q000494:pharmacology
chemical_list: D000577:Amides; D018949:Antigens, CD1; C088670:BB 2116; C093640:CT 1166; D006241:Haptens; D006877:Hydroxamic Acids; D009025:Morpholines; D011480:Protease Inhibitors; D013876:Thiophenes; D010649:Phenylalanine; C029938:nickel sulfate; D009532:Nickel; C080985:batimastat; D008666:Metalloendopeptidases