A critical role for prostaglandin E2 in podosome dissolution and induction of high-speed migration during dendritic cell maturation.

van Helden SF, Krooshoop DJ, Broers KC, Raymakers RA, Figdor CG, van Leeuwen FN
J Immunol. 2006 Aug 1;177(3):1567-74.

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.

URL: http://www.jimmunol.org/cgi/content/full/177/3/1567

Pub Med: http://www.ncbi.nlm.nih.gov/pubmed/16849464

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