PMID- 24268109 OWN - NLM STAT- MEDLINE DCOM- 20141001 LR - 20140203 IS - 1878-3279 (Electronic) IS - 0171-2985 (Linking) VI - 219 IP - 3 DP - 2014 Mar TI - Chemokines and other GPCR ligands synergize in receptor-mediated migration of monocyte-derived immature and mature dendritic cells. PG - 218-29 LID - S0171-2985(13)00187-3 [pii] LID - 10.1016/j.imbio.2013.10.004 [doi] AB - Dendritic cells (DCs) are potent antigen presenting cells, described as the initiators of adaptive immune responses. Immature monocyte-derived DCs (MDDC) showed decreased CD14 expression, increased cell surface markers DC-SIGN and CD1a and enhanced levels of receptors for the chemokines CCL3 (CCR1/CCR5) and CXCL8 (CXCR1/CXCR2) compared with human CD14(+) monocytes. After further MDDC maturation by LPS, the markers CD80 and CD83 and the chemokine receptors CXCR4 and CCR7 were upregulated, whereas CCR1, CCR2 and CCR5 expression was reduced. CCL3 dose-dependently synergized with CXCL8 or CXCL12 in chemotaxis of immature MDDC. CXCL12 augmented the CCL3-induced ERK1/2 and Akt phosphorylation in immature MDDC, although the synergy between CCL3 and CXCL12 in chemotaxis of immature MDDC was dependent on the Akt signaling pathway but not on ERK1/2 phosphorylation. CCL2 also synergized with CXCL12 in immature MDDC migration. Moreover, two CXC chemokines not sharing receptors (CXCL12 and CXCL8) cooperated in immature MDDC chemotaxis, whereas two CC chemokines (CCL3 and CCL7) sharing CCR1 did not. Further, the non-chemokine G protein-coupled receptor ligands chemerin and fMLP synergized with respectively CCL7 and CCL3 in immature MDDC signaling and migration. Finally, CXCL12 and CCL3 did not cooperate, but CXCL12 synergized with CCL21 in mature MDDC chemotaxis. Thus, chemokine synergy in immature and mature MDDC migration is dose-dependently regulated by chemokines via alterations in their chemokine receptor expression pattern according to their role in immune responses. CI - Copyright (c) 2013 Elsevier GmbH. All rights reserved. FAU - Gouwy, Mieke AU - Gouwy M AD - Laboratory of Molecular Immunology, Rega Institute for Medical Research, Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium. FAU - Struyf, Sofie AU - Struyf S AD - Laboratory of Molecular Immunology, Rega Institute for Medical Research, Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium. FAU - Leutenez, Lien AU - Leutenez L AD - Laboratory of Molecular Immunology, Rega Institute for Medical Research, Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium. FAU - Portner, Noemie AU - Portner N AD - Laboratory of Molecular Immunology, Rega Institute for Medical Research, Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium. FAU - Sozzani, Silvano AU - Sozzani S AD - Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy; Humanitas Clinical and Research Center, Rozzano, Italy. FAU - Van Damme, Jo AU - Van Damme J AD - Laboratory of Molecular Immunology, Rega Institute for Medical Research, Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium. Electronic address: jo.vandamme@rega.kuleuven.be. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131014 PL - Netherlands TA - Immunobiology JT - Immunobiology JID - 8002742 RN - 0 (Antigens, CD) RN - 0 (Chemokines) RN - 0 (Receptors, Chemokine) RN - 0 (Receptors, G-Protein-Coupled) RN - EC 2.7.11.1 (Oncogene Protein v-akt) SB - IM MH - Adaptive Immunity MH - Antigens, CD/metabolism MH - Cell Differentiation MH - Cells, Cultured MH - Chemokines/*metabolism MH - Chemotaxis MH - Dendritic Cells/*immunology MH - Humans MH - Immunity, Innate MH - Monocytes/*immunology MH - Oncogene Protein v-akt/metabolism MH - Receptor Cross-Talk MH - Receptors, Chemokine/genetics/*metabolism MH - Receptors, G-Protein-Coupled/genetics/*metabolism MH - Signal Transduction OTO - NOTNLM OT - BCA OT - CAM OT - CC chemokine ligand OT - CCL OT - CI OT - CXC chemokine ligand OT - CXCL OT - Chemoattractants OT - ERK OT - G protein-coupled receptor OT - GAG OT - GM-CSF OT - GPCR OT - LPS OT - MACS OT - MAPK OT - MDDC OT - MFI OT - Maturation OT - Migration OT - PBMC OT - PHA OT - Receptor expression OT - SEM OT - Signal transduction OT - Synergy OT - bicinchoninic acid OT - cell-adhesion molecules OT - chemotactic index OT - extracellular signal-regulated kinase OT - glycosaminoglycans OT - granulocyte-macrophage colony stimulating factor OT - lipopolysaccharide OT - magnetic cell sorting OT - mean fluorescence intensity OT - mitogen-activated protein kinase OT - monocyte-derived dendritic cells OT - peripheral blood mononuclear cells OT - phytohemagglutinin OT - standard error of the mean EDAT- 2013/11/26 06:00 MHDA- 2014/10/02 06:00 CRDT- 2013/11/26 06:00 PHST- 2013/05/22 00:00 [received] PHST- 2013/09/27 00:00 [revised] PHST- 2013/10/07 00:00 [accepted] PHST- 2013/11/26 06:00 [entrez] PHST- 2013/11/26 06:00 [pubmed] PHST- 2014/10/02 06:00 [medline] AID - S0171-2985(13)00187-3 [pii] AID - 10.1016/j.imbio.2013.10.004 [doi] PST - ppublish SO - Immunobiology. 2014 Mar;219(3):218-29. doi: 10.1016/j.imbio.2013.10.004. Epub 2013 Oct 14.