PMID- 16849464 OWN - NLM STAT- MEDLINE DCOM- 20060906 LR - 20190516 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 177 IP - 3 DP - 2006 Aug 1 TI - A critical role for prostaglandin E2 in podosome dissolution and induction of high-speed migration during dendritic cell maturation. PG - 1567-74 AB - 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. FAU - van Helden, Suzanne F G AU - van Helden SF AD - Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; FAU - Krooshoop, Danielle J E B AU - Krooshoop DJ FAU - Broers, Karin C M AU - Broers KC FAU - Raymakers, Reinier A P AU - Raymakers RA FAU - Figdor, Carl G AU - Figdor CG FAU - van Leeuwen, Frank N AU - van Leeuwen FN LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Integrin alpha5beta1) RN - 0 (Lipopolysaccharides) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Cell Adhesion/immunology MH - *Cell Differentiation/immunology MH - *Cell Movement/immunology MH - Cell Surface Extensions/immunology/*metabolism MH - Dendritic Cells/*cytology/*metabolism MH - Dinoprostone/biosynthesis/*physiology MH - Humans MH - Integrin alpha5beta1/antagonists & inhibitors/metabolism/physiology MH - Lipopolysaccharides/pharmacology MH - Myeloid Progenitor Cells/cytology/metabolism MH - Signal Transduction/immunology MH - Time Factors EDAT- 2006/07/20 09:00 MHDA- 2006/09/07 09:00 CRDT- 2006/07/20 09:00 PHST- 2006/07/20 09:00 [pubmed] PHST- 2006/09/07 09:00 [medline] PHST- 2006/07/20 09:00 [entrez] AID - 177/3/1567 [pii] AID - 10.4049/jimmunol.177.3.1567 [doi] PST - ppublish SO - J Immunol. 2006 Aug 1;177(3):1567-74. doi: 10.4049/jimmunol.177.3.1567.