Cardiac Allograft Rejection: Examination of the Expression and Function of the Decoy Chemokine Receptor D6

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. 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. D6 expression was found to be higher in the biopsies taken from more severe cardiac allograft rejection (P