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Titolo:
ALPHA(6) INTEGRINS ARE REQUIRED FOR LANGERHANS CELL-MIGRATION FROM THE EPIDERMIS
Autore:
PRICE AA; CUMBERBATCH M; KIMBER I; AGER A;
Indirizzi:
NATL INST MED RES,DIV CELLULAR IMMUNOL,MILL HILL LONDON NW7 1AA ENGLAND NATL INST MED RES,DIV CELLULAR IMMUNOL LONDON NW7 1AA ENGLAND ZENECA CENT TOXICOL LAB MACCLESFIELD SK10 4TJ CHESHIRE ENGLAND
Titolo Testata:
The Journal of experimental medicine
fascicolo: 10, volume: 186, anno: 1997,
pagine: 1725 - 1735
SICI:
0022-1007(1997)186:10<1725:AIARFL>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
DRAINING LYMPH-NODES; NECROSIS-FACTOR-ALPHA; COLONY-STIMULATING FACTOR; DENDRITIC CELLS; INTERDIGITATING CELLS; ADHESION MOLECULES; LAMININ; HEMIDESMOSOMES; LYMPHOCYTES; SURFACE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
42
Recensione:
Indirizzi per estratti:
Citazione:
A.A. Price et al., "ALPHA(6) INTEGRINS ARE REQUIRED FOR LANGERHANS CELL-MIGRATION FROM THE EPIDERMIS", The Journal of experimental medicine, 186(10), 1997, pp. 1725-1735

Abstract

Topical exposure of mice to chemical allergens results in the migration of epidermal Langerhans cells (LCs) from the skin and their accumulation as immunostimulatory dendritic cells (DCs) in draining lymph nodes. Epidermal cell-derived cytokines have been implicated in the maturation and migration of LCs, but the adhesion molecules that regulate LC migration have not been studied. We hypothesized that integrin-mediated interactions with extracellular matrix components of the skin and lymph node may regulate LC/DC migration. We found that alpha(6) integrins and alpha(4) integrins were differentially expressed by epidermal LCs and lymph node DCs. A majority of LCs (70%) expressed the alpha(6)integrin subunit, whereas DCs did not express alpha(6) integrins. In contrast, the alpha(6) integrin subunit was expressed at high levels on DCs but at much lower levels on LCs. The anti-alpha(6) integrin antibody, GoH3, which blocks binding to laminin, completely prevented the spontaneous migration of LCs from skin explants in vitro and the rapidmigration of LCs from mouse ear skin induced after intradermal administration of TNF-alpha in vivo. GoH3 also reduced the accumulation of DCs in draining lymph nodes by a maximum of 70% after topical administration of the chemical allergen oxazolone. LCs remaining in the epidermis in the presence of GoH3 adopted a rounded morphology, rather than the interdigitating appearance typical of LCs in naive skin, suggestingthat the cells had detached from neighboring keratinocytes and withdrawn cellular processes in preparation for migration, but were unable to leave the epidermis. The anti-alpha(4) integrin antibody PS/2, whichblocks binding to fibronectin, had no effect on LC migration from theepidermis either in vitro or in vivo, or on the accumulation of DCs in draining lymph nodes after oxazolone application. RGD-containing peptides were also without effect on LC migration from skin explants. These results identify an important role for alpha(6) integrins in the migration of LC from the epidermis to the draining lymph node by regulating access across the epidermal basement membrane. In contrast, alpha(4) integrins, or other integrin-dependent interactions with fibronectin that are mediated by the RGD recognition sequence, did not influenceLC migration from the epidermis. In addition, alpha(4) integrins did not affect the accumulation of LCs as DCs in draining lymph nodes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 02:17:31