title: Evidence that CXCL16 is a potent mediator of angiogenesis and is involved in endothelial progenitor cell chemotaxis : studies in mice with K/BxN serum-induced arthritis.
abstract: OBJECTIVE
  To examine the possibility that CXCL16 recruits endothelial cells (ECs) to developing neovasculature in rheumatoid arthritis (RA) synovium.
  
  
  METHODS
  We utilized the RA synovial tissue SCID mouse chimera system to examine human microvascular EC (HMVEC) and human endothelial progenitor cell (EPC) recruitment into engrafted human synovium that was injected intragraft with CXCL16-immunodepleted RA synovial fluid (SF). CXCR6-deficient and wild-type (WT) C57BL/6 mice were primed to develop K/BxN serum-induced arthritis and evaluated for angiogenesis. HMVECs and EPCs from human cord blood were also examined for CXCR6 expression, by immunofluorescence and assessment of CXCL16 signaling activity.
  
  
  RESULTS
  CXCR6 was prominently expressed on human EPCs and HMVECs, and its expression on HMVECs could be up-regulated by interleukin-1β. SCID mice injected with CXCL16-depleted RA SF exhibited a significant reduction in EPC recruitment. In experiments using the K/BxN serum-induced inflammatory arthritis model, CXCR6(-/-) mice showed profound reductions in hemoglobin levels, which correlated with reductions in monocyte and T cell recruitment to arthritic joint tissue compared to that observed in WT mice. Additionally, HMVECs and EPCs responded to CXCL16 stimulation, but exhibited unique signal transduction pathways and homing properties.
  
  
  CONCLUSIONS
  These results indicate that CXCL16 and its receptor CXCR6 may be a central ligand/receptor pair that is closely associated with EPC recruitment and blood vessel formation in the RA joint.
authors: University of Michigan Medical School, Ann Arbor, MI, USA.
authors: Takeo
authors: T
authors: Isozaki
authors: Ali S
authors: AS
authors: Arbab
authors: Christian S
authors: CS
authors: Haas
authors: M Asif
authors: MA
authors: Amin
authors: Monica D
authors: MD
authors: Arendt
authors: Alisa E
authors: AE
authors: Koch
authors: Jeffrey H
authors: JH
authors: Ruth
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000503:physiopathology; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000502:physiology*; D019743:Chemokines, CXC / Q000502:physiology*; D002633:Chemotaxis / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000503:physiopathology; D054387:Receptors, CXCR / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000378:metabolism / Q000502:physiology*; D051116:Receptors, Scavenger / Q000502:physiology*; D011991:Receptors, Virus / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000502:physiology; D013583:Synovial Membrane / Q000378:metabolism
chemical_list: C423727:CXCL16 protein, human; C106330:CXCR6 protein, human; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; C498926:Cxcl16 protein, mouse; C482906:Cxcr6 protein, mouse; D053583:Interleukin-1beta; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D051116:Receptors, Scavenger; D011991:Receptors, Virus
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