TY - JOUR
T1 - A critical role for prostaglandin E2 in podosome dissolution and induction of high-speed migration during dendritic cell maturation
AU - van Helden, Suzanne F G
AU - Krooshoop, Daniëlle J E B
AU - Broers, Karin C M
AU - Raymakers, Reinier A P
AU - Figdor, Carl G
AU - van Leeuwen, Frank N
PY - 2006/8/1
Y1 - 2006/8/1
N2 - 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.
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.
KW - Cell Adhesion/immunology
KW - Cell Differentiation/immunology
KW - Cell Movement/immunology
KW - Cell Surface Extensions/immunology
KW - Dendritic Cells/cytology
KW - Dinoprostone/biosynthesis
KW - Humans
KW - Integrin alpha5beta1/antagonists & inhibitors
KW - Lipopolysaccharides/pharmacology
KW - Myeloid Progenitor Cells/cytology
KW - Signal Transduction/immunology
KW - Time Factors
UR - http://www.scopus.com/inward/record.url?scp=33746210274&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.177.3.1567
DO - 10.4049/jimmunol.177.3.1567
M3 - Article
C2 - 16849464
SN - 0022-1767
VL - 177
SP - 1567
EP - 1574
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -