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

Bradford, L., Marshall, H., Robertson, H., Kirby, J. A., Graham, G. , Ali, S. and O'Boyle, G. (2010) Cardiac Allograft Rejection: Examination of the Expression and Function of the Decoy Chemokine Receptor D6. Transplantation, 89(11), pp. 1411-1416. (doi:10.1097/TP.0b013e3181da604b)

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Publisher's URL: http://dx.doi.org/10.1097/TP.0b013e3181da604b

Abstract

<b>Background:</b> 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.<p></p> <b>Methods:</b> 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.<p></p> <b>Results:</b> 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-β strongly increased the expression of D6 by monocytes, which significantly enhanced D6-mediated chemokine scavenging (by 85%, P<0.05).<p></p> <b>Conclusions:</b> 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-β. Understanding the expression patterns of D6 may provide important insight into the regulation and control of inflammatory cell recruitment during allograft rejection.<p></p>

Item Type:Articles
Keywords:ARTERIOSCLEROSIS ASSAY BETA BINDING BIOLOGY Chemokine CLONING CYTOKINES D6 Decoy DNA endothelium ENGLAND EXPRESSION growth HEART Human immunity IN-VITRO inflammation MECHANISM MONOCYTES MS PATTERN PATTERNS RECEPTOR RECEPTOR D6 RECRUITMENT RENAL-TRANSPLANT REJECTION SURFACE SURGERY TRENDS TUMORS
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Graham, Professor Gerard
Authors: Bradford, L., Marshall, H., Robertson, H., Kirby, J. A., Graham, G., Ali, S., and O'Boyle, G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Transplantation
Publisher:Lippincott Williams & Wilkins
ISSN:0041-1337
ISSN (Online):1534-6080
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
514422Regulation of the adaptive immune response by chemokine scavenging receptorsGerard GrahamMedical Research Council (MRC)G0901113Infection Immunity and Inflammation Medicine