Influence of ERK activation on decreased chemotaxis of mature human cord blood monocyte-derived dendritic cells to CCL19 and CXCL12.
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.
Li
Geling
G
Department of Microbiology and Immunology, Walther Oncology Center, Indiana University School of Medicine, 950 West Walnut Street, Indianapolis, IN 46202, USA.
Basu
Sunanda
S
Han
Myung-Kwan
MK
Kim
Young-June
YJ
Broxmeyer
Hal E
HE
D002478:Cells, Cultured; D054415:Chemokine CCL19; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D036101:Cord Blood Stem Cell Transplantation; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D054400:Receptors, CCR7; D019718:Receptors, CXCR4 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism
C515460:CCL19 protein, human; C515370:CCR7 protein, human; C515255:CXCL12 protein, human; D054415:Chemokine CCL19; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; D008070:Lipopolysaccharides; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D048049:Extracellular Signal-Regulated MAP Kinases