title: CCR and CC chemokine expression in relation to Flt3 ligand-induced renal dendritic cell mobilization.
abstract: BACKGROUND
  We investigated the expression and function of CC chemokine receptors (CCR) on highly-purified kidney and blood dendritic cells isolated from mice in which dendritic cells were mobilized with fms-like tyrosine 3 kinase ligand (Flt3L).
  
  
  METHODS
  CCR and CC chemokine expression were determined by RNase protection assay or flow cytometry, and dendritic cell migratory responses assayed using Transwell chambers. Chemokine production in renal tissue was detected by immunofluorescence staining. Trafficking of fluorochrome-labeled dendritic cells was monitored in vivo.
  
  
  RESULTS
  Freshly-isolated renal dendritic cells expressed mRNA for CCR1, 2, 5, and 7 and CCR1 and 5 protein. They did not migrate to inducible chemokines--CCL3 [macrophage inflammatory protein (MIP)-1alpha], CCL5 [regulated upon activation, normal T cell expressed and secreted (RANTES)], or CCL20 (MIP-3alpha). Following lipopolysaccharide (LPS) stimulation, the dendritic cells down-regulated CCR1, 2, and 5 expression, up-regulated or sustained signals for CCR7, and migrated to the constitutively expressed ligands CCL19 (MIP-3beta) and CCL21 (secondary lymphoid tissue chemokine). Normal kidneys expressed weak message for CCL2, 3, and 4, with stronger signals for CCL5 and 19. Intrarenal CCL5 production was enhanced by Flt3L administration, in association with marked increases in interstitial CD45+ mononuclear cells. Mobilized blood dendritic cells migrated to CCR2 and CCR5 ligands and trafficked to renal intertubular sites following adoptive (intravenous) transfer. Their migration to the CCR5 ligand MIP-1beta (CCL4) and homing to kidneys of Flt3L-treated recipients were inhibited by CCR5 antagonism.
  
  
  CONCLUSIONS
  These data implicate specific CCR and their ligands in regulation of the dendritic cell constituency of the kidney. CCR5 antagonism inhibits their directed migration and intrarenal accumulation.
authors.affiliation: Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: P Toby H
authors.initials: PT
authors.lastname: Coates
authors.forename: Bridget L
authors.initials: BL
authors.lastname: Colvin
authors.forename: Anju
authors.initials: A
authors.lastname: Ranganathan
authors.forename: F Jason
authors.initials: FJ
authors.lastname: Duncan
authors.forename: Yuk Yuen
authors.initials: YY
authors.lastname: Lan
authors.forename: William J
authors.initials: WJ
authors.lastname: Shufesky
authors.forename: Alan F
authors.initials: AF
authors.lastname: Zahorchak
authors.forename: Adrian E
authors.initials: AE
authors.lastname: Morelli
authors.forename: Angus W
authors.initials: AW
authors.lastname: Thomson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001773:Blood Cells / Q000378:metabolism / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology; D018946:Chemokine CCL5 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects*; D003713:Dendritic Cells / Q000378:metabolism / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007668:Kidney / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D013154:Spleen; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; C515301:Ccr1 protein, mouse; C515335:Ccr2 protein, mouse; D018946:Chemokine CCL5; D019742:Chemokines, CC; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012333:RNA, Messenger; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; C084881:flt3 ligand protein