title: Signaling events following chemokine receptor ligation in human dendritic cells at different developmental stages.
abstract: Responsiveness of dendritic cells (DC) to inflammatory CC chemokines is down-regulated during their maturation. We analyzed the mechanism underlying these events. Cell-surface expression of CC chemokine receptor (CCR)-1, -3 and -5 was increased during differentiation of immature DC (iDC) from monocytes. In contrast, these expressions were decreased during development of iDC into mature DC (mDC) to levels similar to those of monocytes. Transcriptional expression of CCR-1, -3 and -5 was increased during differentiation of iDC from monocytes, while the expression was decreased during development of iDC into mDC. Expression of CCR-7 transcript was detected in mDC, but not in monocytes or iDC. Both monocytes and iDC, but not mDC, migrated in response to inflammatory CC chemokines such as regulated on activation normal T cell expressed and secreted (RANTES)/CCL5, whereas mDC, but not monocytes or iDC, migrated to macrophage inflammatory protein (MIP)-3ss/CCL19. Receptor engagement of monocytes or iDC by RANTES (for CCR-1, -3 and -5) resulted in protein tyrosine phosphorylation events including activation of focal adhesion kinase as well as mitogen-activated protein kinase, whereas this stimulation induced little activation of these molecular events in mDC when compared with monocytes or iDC. On the other hand, stimulation with MIP-3ss (for CCR-7) induced tyrosine phosphorylation events in mDC, but not in monocytes or iDC. These results suggest that the down-regulation of cell-surface expression of CCR and of their downstream signaling events may be involved in the reduced chemotaxis of DC to inflammatory CC chemokines during their maturation.
authors.affiliation: Department of Cell Processing, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Kawasaki
authors.forename: H
authors.initials: H
authors.lastname: Nagayama
authors.forename: M
authors.initials: M
authors.lastname: Enomoto
authors.forename: C
authors.initials: C
authors.lastname: Morimoto
authors.forename: K
authors.initials: K
authors.lastname: Tadokoro
authors.forename: T
authors.initials: T
authors.lastname: Juji
authors.forename: T A
authors.initials: TA
authors.lastname: Takahashi
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D054415:Chemokine CCL19; D018946:Chemokine CCL5 / Q000502:physiology; D019742:Chemokines, CC / Q000378:metabolism / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D051417:Focal Adhesion Kinase 1; D051418:Focal Adhesion Kinase 2; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: C515460:CCL19 protein, human; D054415:Chemokine CCL19; D018946:Chemokine CCL5; D019742:Chemokines, CC; D007457:Iodine Radioisotopes; D019707:Receptors, Chemokine; D010566:Virulence Factors, Bordetella; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051418:Focal Adhesion Kinase 2; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases