In vitro adhesion of human epidermal Langerhans cells to laminin and fibronectin occurs through beta 1 integrin receptors.
Human epidermal Langerhans cells are dendritic cells that can capture, process, and present antigens to T cells. It was previously shown that these Langerhans cells express the very late activation antigen (VLA) protein family of beta 1 integrins. beta 1 integrins mainly mediate the adhesion of cells to a number of extracellular components, such as laminin, fibronectin, and collagen, which are present in the skin. In this report, we demonstrate that a large percentage of the Langerhans cell population was able in vitro to attach to laminin and fibronectin but not to collagen. An ultrastructural study of adherent Langerhans cells showed that they were spread largely on laminin, with a loss of their round shape, and partially on fibronectin. Langerhans cell binding to laminin or fibronectin induced a decrease of the Birbeck granule number. Specific inhibitions of cell adhesion were performed, and it was demonstrated that VLA-6 was the major receptor involved in Langerhans cell adhesion to laminin. This adhesion was not RGD dependent and was slightly enhanced by Mn2+. VLA-3 and especially VLA-5 mediated Langerhans cell binding to fibronectin through the RGDS sequence of the protein. Mn2+ sharply increased the Langerhans cell adhesion to fibronectin. VLA-6 mediated in vitro Langerhans cell adhesion to laminin, which suggests that in vivo VLA-6 could permit Langerhans cells to attach and migrate through the basement membrane. Moreover, VLA-5 and VLA-3 take part in the in vitro Langerhans cell binding to fibronectin, suggesting that in vivo these fibronectin receptors could facilitate Langerhans cell passage throughout the fibronectin network of the dermis before migration to lymph nodes.
Le Varlet
B
B
INSERM U209, Clinique Dermatologique, Hôpital Ed. Herriot, Lyon, France.
Staquet
M J
MJ
Dezutter-Dambuyant
C
C
Delorme
P
P
Schmitt
D
D
D000595:Amino Acid Sequence; D002448:Cell Adhesion; D003094:Collagen / Q000378:metabolism; D000078404:Epidermal Cells; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000378:metabolism; D007801:Langerhans Cells / Q000166:cytology*; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D018000:Receptors, Peptide; D016029:Receptors, Very Late Antigen / Q000378:metabolism*
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D010455:Peptides; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D016029:Receptors, Very Late Antigen; C051382:arginyl-glycyl-aspartic acid directed cell adhesion receptor; D003094:Collagen