title: Inhibition of CXCR3-mediated chemotaxis by the human chemokine receptor-like protein CCX-CKR.
abstract: OBJECTIVE
  Induction of cellular migration is the primary effect of chemokine receptor activation. However, several chemokine receptor-like proteins bind chemokines without subsequent induction of intracellular signalling and chemotaxis. It has been suggested that they act as chemokine scavengers, which may control local chemokine levels and contribute to the function of chemokines during inflammation. This has been verified for the chemokine-like receptor proteins D6 and DARC as well as CCX-CKR. Here, we provide evidence for an additional biological function of human (h)CCX-CKR.
  
  
  METHODS
  We used transfection strategies in HEK293 and human T cells.
  
  
  RESULTS
  Co-expression of hCCX-CKR completely inhibits hCXCR3-induced chemotaxis. We found that hCCX-CKR forms complexes with hCXCR3, suggesting a relationship between CCX-CKR heteromerization and inhibition of chemotaxis. Moreover, negative binding cooperativity induced by ligands both for hCXCR3 and hCCX-CKR was observed in cells expressing both receptors. This negative cooperativity may also explain the hCCX-CKR-induced inhibition of chemotaxis.
  
  
  CONCLUSIONS
  These findings suggest that hCCX-CKR prevents hCXCR3-induced chemotaxis by heteromerization thus representing a novel mechanism of regulation of immune cell migration.
authors.affiliation: Department of Neuroscience, Section Medical Physiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Vinet
authors.forename: M
authors.initials: M
authors.lastname: van Zwam
authors.forename: I M
authors.initials: IM
authors.lastname: Dijkstra
authors.forename: N
authors.initials: N
authors.lastname: Brouwer
authors.forename: H R J
authors.initials: HR
authors.lastname: van Weering
authors.forename: A
authors.initials: A
authors.lastname: Watts
authors.forename: M
authors.initials: M
authors.lastname: Meijer
authors.forename: M R
authors.initials: MR
authors.lastname: Fokkens
authors.forename: V
authors.initials: V
authors.lastname: Kannan
authors.forename: D
authors.initials: D
authors.lastname: Verzijl
authors.forename: H F
authors.initials: HF
authors.lastname: Vischer
authors.forename: M J
authors.initials: MJ
authors.lastname: Smit
authors.forename: R
authors.initials: R
authors.lastname: Leurs
authors.forename: K
authors.initials: K
authors.lastname: Biber
authors.forename: H W G M
authors.initials: HW
authors.lastname: Boddeke
mesh_terms: D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D015536:Down-Regulation; D031541:Fluorescence Resonance Energy Transfer; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D008024:Ligands; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D021381:Protein Transport; D012333:RNA, Messenger; D054388:Receptors, CCR / Q000235:genetics / Q000378:metabolism*; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: C408223:ACKR4 protein, human; C515187:CXCR3 protein, human; D018925:Chemokines; D008024:Ligands; D008164:Luminescent Proteins; D012333:RNA, Messenger; D054388:Receptors, CCR; D054367:Receptors, CXCR3; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins