title: Cardiac allograft rejection: examination of the expression and function of the decoy chemokine receptor D6.
abstract: BACKGROUND
  Inflammatory cell recruitment during allograft rejection is driven by a group of inflammatory cytokines termed chemokines. Chemokines are presented on the surface of the vascular endothelium where they ligate specific receptors expressed on the surface of leukocytes. Recently, a group of nonsignaling chemokine receptors have been described. These bind and internalize chemokines but do not drive leukocyte migration. It is believed that these compete with classical signaling receptors to modulate inflammation.
  
  
  METHODS
  This study describes the first examination of the human decoy chemokine receptor D6 during rejection; D6 binds at least 12 potent proinflammatory chemokines. The expression of D6 by graft infiltrating leukocytes was examined in cardiac allografts by confocal microscopy on biopsy sections (n=19). Cytokine regulation of D6 was examined in vitro, and a chemokine scavenging assay was performed using the prototypical transplant-associated chemokine CCL5/RANTES.
  
  
  RESULTS
  D6 expression was found to be higher in the biopsies taken from more severe cardiac allograft rejection (P<0.01) and was predominantly localized to graft infiltrating CD45(+)CD68(+) leukocytes. In vitro studies demonstrated that the transforming growth factor-beta strongly increased the expression of D6 by monocytes, which significantly enhanced D6-mediated chemokine scavenging (by 85%, P<0.05).
  
  
  CONCLUSIONS
  We present the first examination of the biology of D6 during rejection and identify a transplant-associated cytokine that is able to regulate its expression. These data suggest an exciting new mechanism for the antiinflammatory actions of transforming growth factor-beta. Understanding the expression patterns of D6 may provide important insight into the regulation and control of inflammatory cell recruitment during allograft rejection.
authors.affiliation: Applied Immunobiology and Transplantation Research Group, Insitute of Cellular Medicine, Newcastle University, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Bradford
authors.forename: Helen
authors.initials: H
authors.lastname: Marshall
authors.forename: Helen
authors.initials: H
authors.lastname: Robertson
authors.forename: John A
authors.initials: JA
authors.lastname: Kirby
authors.forename: Gerard
authors.initials: G
authors.lastname: Graham
authors.forename: Sim
authors.initials: S
authors.lastname: Ali
authors.forename: Graeme
authors.initials: G
authors.lastname: O'Boyle
mesh_terms: D000818:Animals; D001706:Biopsy; D002460:Cell Line; D016207:Cytokines / Q000276:immunology / Q000502:physiology; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D023421:Models, Animal; D009000:Monocytes / Q000502:physiology; D051381:Rats; D054447:Receptors, CCR10 / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D019707:Receptors, Chemokine / Q000502:physiology; D014184:Transplantation, Homologous / Q000276:immunology; D000097628:Chemokine Receptor D6
chemical_list: D016207:Cytokines; D054447:Receptors, CCR10; D019707:Receptors, Chemokine; D000097628:Chemokine Receptor D6