PMID- 17179222 OWN - NLM STAT- MEDLINE DCOM- 20070523 LR - 20210206 IS - 0006-4971 (Print) IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 109 IP - 8 DP - 2007 Apr 15 TI - Influence of ERK activation on decreased chemotaxis of mature human cord blood monocyte-derived dendritic cells to CCL19 and CXCL12. PG - 3173-6 AB - 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. FAU - Li, Geling AU - Li G AD - Department of Microbiology and Immunology, Walther Oncology Center, Indiana University School of Medicine, 950 West Walnut Street, Indianapolis, IN 46202, USA. FAU - Basu, Sunanda AU - Basu S FAU - Han, Myung-Kwan AU - Han MK FAU - Kim, Young-June AU - Kim YJ FAU - Broxmeyer, Hal E AU - Broxmeyer HE LA - eng GR - P01 HL 053586/HL/NHLBI NIH HHS/United States GR - R01 HL 56416/HL/NHLBI NIH HHS/United States GR - R01 HL 67384/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20061219 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (CCL19 protein, human) RN - 0 (CCR7 protein, human) RN - 0 (CXCL12 protein, human) RN - 0 (Chemokine CCL19) RN - 0 (Chemokine CXCL12) RN - 0 (Chemokines, CC) RN - 0 (Chemokines, CXC) RN - 0 (Lipopolysaccharides) RN - 0 (Receptors, CCR7) RN - 0 (Receptors, CXCR4) RN - 0 (Receptors, Chemokine) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Cells, Cultured MH - Chemokine CCL19 MH - Chemokine CXCL12 MH - Chemokines, CC/*metabolism MH - Chemokines, CXC/*metabolism MH - Chemotaxis/drug effects/*physiology MH - Cord Blood Stem Cell Transplantation MH - Dendritic Cells/cytology/*metabolism MH - Enzyme Activation/drug effects/physiology MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Fetal Blood/cytology/*metabolism MH - Humans MH - Lipopolysaccharides/pharmacology MH - MAP Kinase Signaling System/drug effects/*physiology MH - Monocytes/cytology/*metabolism MH - Receptors, CCR7 MH - Receptors, CXCR4/metabolism MH - Receptors, Chemokine/metabolism PMC - PMC1852231 EDAT- 2006/12/21 09:00 MHDA- 2007/05/24 09:00 PMCR- 2008/04/15 CRDT- 2006/12/21 09:00 PHST- 2006/12/21 09:00 [pubmed] PHST- 2007/05/24 09:00 [medline] PHST- 2006/12/21 09:00 [entrez] PHST- 2008/04/15 00:00 [pmc-release] AID - S0006-4971(20)41686-6 [pii] AID - 2006/014753 [pii] AID - 10.1182/blood-2006-04-014753 [doi] PST - ppublish SO - Blood. 2007 Apr 15;109(8):3173-6. doi: 10.1182/blood-2006-04-014753. Epub 2006 Dec 19.