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 Blood, 15 April 2007, Vol. 109, No. 8, pp. 3173-3176.
Prepublished online as a Blood First Edition Paper on December 19, 2006; DOI 10.1182/blood-2006-04-014753.

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CHEMOKINES, CYTOKINES, AND INTERLEUKINS

Brief Report

Influence of ERK activation on decreased chemotaxis of mature human cord blood monocyte–derived dendritic cells to CCL19 and CXCL12

Geling Li1,2, Sunanda Basu1,2, Myung-Kwan Han1,2, Young-June Kim1,2, and Hal E. Broxmeyer1,2

1 Department of Microbiology and Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis; 2 Walther Cancer Institute, Indianapolis, IN

Dendritic cells (DCs) 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 DCs and maturation agent lipopolysaccharide (LPS)–induced signaling between CB and adult blood (AB). Mature CB DCs expressed reduced CCR7, but increased CXCR4. This was associated with reduced migratory efficiency toward both CCR7 ligand CCL19 and CXCR4 ligand CXCL12. LPS induced higher extracellular signal-regulated kinase (ERK) phosphorylation in CB than in AB DCs. Specific inhibition of ERK during CB DC maturation enhanced LPS-induced up-regulation of CCR7 and CXCR4 on CB DCs and their chemotaxis toward CCL19 and CXCL12, to a level similar to that of mature AB DCs. Overall, monocyte-derived CB DCs responded to LPS with stronger and sustained ERK activation, which negatively correlated with LPS-induced up-regulation of CCR7 and CXCR4 on CB DCs and their migratory responses. These findings may have potential relevance to better understanding DC function in CB transplantation.


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