title: A critical role for prostaglandin E2 in podosome dissolution and induction of high-speed migration during dendritic cell maturation.
abstract: 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.
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands;
authors.forename: Suzanne F G
authors.initials: SF
authors.lastname: van Helden
authors.forename: Daniëlle J E B
authors.initials: DJ
authors.lastname: Krooshoop
authors.forename: Karin C M
authors.initials: KC
authors.lastname: Broers
authors.forename: Reinier A P
authors.initials: RA
authors.lastname: Raymakers
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.forename: Frank N
authors.initials: FN
authors.lastname: van Leeuwen
mesh_terms: 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
chemical_list: D039081:Integrin alpha5beta1; D008070:Lipopolysaccharides; D015232:Dinoprostone