Human epidermal Langerhans cells express beta 1 integrins that mediate their adhesion to laminin and fibronectin.
Members of the beta 1 or very late antigen (VLA) integrin family represent the predominant class of integrin extracellular matrix receptors. Adhesion assays were developed for the identification of the beta 1 integrins involved in the adhesive interactions between Langerhans cells (which mainly express alpha 4 beta 1, alpha 5 beta 1, and alpha 6 beta 1) and extracellular matrix proteins. For this purpose, binding assays were performed on fibronectin-, laminin-, collagen type IV-, and collagen type I-coated plates. 59% +/- 21% of Langerhans cells (LC) specifically attached to fibronectin. Using as inhibitory probes monoclonal antibodies against the beta 1, alpha 5, and alpha 3 chains and the synthetic peptide GRGDSP resulted in a decrease of 43%, 41%, 15%, and 42% respectively of LC binding to fibronectin. 76% +/- 20% of LC specifically adhered to laminin. Anti-alpha 6 monoclonal antibody potently inhibited this adhesion, which dropped to 36%, whereas the synthetic peptide GRGDSP was ineffective. A low number of LC adhered to type I and type IV collagen (13-15%). These results indicate that alpha 5 beta 1 and alpha 6 beta 1 were the major beta 1 integrins involved in LC adhesion to fibronectin and laminin. Ultrastructural cell morphology of adherent cells was examined and showed that LC were largely spread on laminin and became tightly bound to the substrate on a large portion of membrane. On fibronectin surface, the contact between LC and substrate was smaller, thus cells could conserve their general round aspect. Moreover, LC binding to fibronectin and laminin induced a significative decrease of the Birbeck granule number. The finding that LC attach to LM and FN in vitro suggests they exist similarly in vivo. By mediating a passage through basement membrane and migration throughout the fibronectin network of the dermis, alpha 5 beta 1 and alpha 6 beta 1 could contribute to the ability of LC to migrate into and out of the epidermis.
Staquet
M J
MJ
INSERM U209, Dermatology Research Unit, E. Herriot Hospital, Lyon, France.
Levarlet
B
B
Dezutter-Dambuyant
C
C
Schmitt
D
D
D002448:Cell Adhesion; D005353:Fibronectins / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007797:Laminin / Q000378:metabolism* / Q000648:ultrastructure; D007801:Langerhans Cells / Q000166:cytology / Q000648:ultrastructure*; D016029:Receptors, Very Late Antigen / Q000502:physiology*
D005353:Fibronectins; D007797:Laminin; D016029:Receptors, Very Late Antigen