Submitted April 3, 2006
Accepted November 27, 2006
Influence of ERK activation on decreased chemotaxis of mature human cord blood monocyte-derived dendritic cells to CCL19 and CXCL12
Geling Li, Sunanda Basu, Myung-Kwan Han, Young-June Kim, and Hal E. Broxmeyer*
Walther Cancer Institute, Indianapolis, IN, United States
Department of Microbiology and Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN, United States
* Corresponding author; email: hbroxmey{at}iupui.edu.
Dendritic cells (DC) are important regulators in graft-versus-host disease (GVHD). To gain insight into cord blood (CB) DC immunology, we compared chemotactic responses of mature monocyte-derived DC and maturation agent LPS-induced signaling between CB and adult blood (AB). Mature CB DC expressed reduced CCR7, but increased CXCR4. This was associated with reduced migratory efficiency towards both CCR7 ligand CCL19 and CXCR4 ligand CXCL12. LPS induced higher ERK phosphorylation in CB, than AB DC. Specific inhibition of ERK during CB DC maturation enhanced LPS-induced up-regulation of CCR7 and CXCR4 on CB DC and their chemotaxis towards CCL19 and CXCL12, to a level similar to that of mature AB DC. Overall, monocyte-derived CB DC responded to LPS with stronger and sustained ERK activation, which negatively correlated with LPS-induced upregulation of CCR7 and CXCR4 on CB DC and their migratory responses. These findings may have potential relevance to better understanding DC function in CB transplantation.
