A critical role for prostaglandin E2 in podosome dissolution and induction of high-speed migration during dendritic cell maturation.
Dendritic cells (DCs) are professional APCs of the immune system that play a key role in regulating T cell-based immunity. The capacity of DCs to activate T cells depends on their maturation state as well as their ability to migrate to the T cell areas of draining lymph nodes. In this study, we investigated the effects of DC maturation stimuli on the actin cytoskeleton and beta(1) integrin-dependent adhesion and migration. Podosomes, specialized adhesion structures found in immature monocyte-derived DCs as well as myeloid DCs, rapidly dissolve in response to maturation stimuli such as TNF-alpha and PGE(2), whereas the TLR agonist LPS induces podosome dissolution only after a long lag time. We demonstrate that LPS-mediated podosome disassembly as well as the onset of high-speed DC migration are dependent on the production of PGs by the DCs. Moreover, both of these processes are inhibited by Ab-induced activation of beta(1) integrins. Together, these results show that maturation-induced podosome dissolution and loss of alpha(5)beta(1) integrin activity allow human DCs to undergo the transition from an adhesive to a highly migratory phenotype.
van Helden
Suzanne F G
SF
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands;
Krooshoop
Daniëlle J E B
DJ
Broers
Karin C M
KC
Raymakers
Reinier A P
RA
Figdor
Carl G
CG
van Leeuwen
Frank N
FN
D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D022081:Cell Surface Extensions / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D039081:Integrin alpha5beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013997:Time Factors
D039081:Integrin alpha5beta1; D008070:Lipopolysaccharides; D015232:Dinoprostone