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Blood, 1 January 2008, Vol. 111, No. 1, pp. 260-270.
Prepublished online as a Blood First Edition Paper on October 9, 2007; DOI 10.1182/blood-2007-05-090613.
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Submitted May 15, 2007
Accepted October 3, 2007
PGE2-induced metalloproteinase-9 is essential for dendritic cell migration
Jui-Hung Yen, Tanzilya Khayrullina, and Doina Ganea*
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA, United States
Department of Biological Sciences, Rutgers University, Newark, NJ, United States
* Corresponding author; email: doina.ganea{at}temple.edu.
Following antigen acquisition and maturation, dendritic cells (DC) disengage from the extracellular matrix, cross basement membranes and travel to draining lymph nodes to activate T cells. CCR7 expression is necessary but not sufficient for the directional migration of DC. PGE2, present in inflammatory sites, induces DC migration, presumably by enacting a migration-permissive gene expression program. Since regulation of DC migration is highly important for their use in vaccination and therapy, we examined the PGE2 induced changes in the expression of metalloproteinases (MMP). Our results indicate that PGE2 significantly upregulates MMP-9 expression, induces both secreted and membrane-bound MMP-9, and that in turn, DC-derived MMP-9 is essential for DC chemotaxis in response to the CCR7 ligand CCL19, Matrigel migration, and in vivo migration in both wild-type and MMP-9-deficient hosts. We conclude that, DC matured within inflammatory sites require both CCR7 and PGE2-induced MMP-9 for their directional migration to draining lymph nodes.
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