The impact of c-met/scatter factor receptor on dendritic cell migration.
Dendritic cells (DC) are professional antigen-presenting cells that possess both migratory properties and potent T cell stimulatory activity, and that allow the uptake of antigenic material inperipheral tissues and its subsequent presentation in the T cell areas of lymphoid organs. Thus motility represents a central property that is required for DC function. Here we report on the expression of the receptor tyrosine kinase c-met in DC. c-Met is the high affinity receptor for scatter factor (SF)/hepatocyte growth factor, and ligand-activated c-met exhibits mitogenic, morphogenic andmotogenic activity in vivo and in vitro. c-Met is signaling competent in DC since it is effectively tyrosine phosphorylated in response to SF ligand. It is demonstrated here that ligand-activated c-met regulates DC adhesion to the extracellular matrix component laminin but leaves antigen presenting function unaffected. Importantly, in ear sheet explant experiments activationof c-met by ligand induces emigration of cutaneous DC (Langerhans cell, LC) from skin, but SF is not a chemoattractant factor for DC. Our results suggest an important role of the c-met/SF system in DC/LC migration.
Max-Delbrück-Center for Molecular Medicine, MDC, Berlin, Germany.
Steffen M
SM
Kurz
Sandra S
SS
Diebold
Thomas
T
Hieronymus
Tatjana C
TC
Gust
Petr
P
Bartunek
Martin
M
Sachs
Walter
W
Birchmeier
Martin
M
Zenke
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D017228:Hepatocyte Growth Factor / Q000276:immunology*; D007797:Laminin / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis / Q000276:immunology*; D012867:Skin / Q000166:cytology
D007797:Laminin; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met