A study of endothelial chemokine binding sites in the rheumatoid synovium

• Main Author: Gardner, Lucy Elizabeth
• Published: Keele University 2005
• Subjects: 616.7227
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.421661

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease resulting in the inflammation of the synovium. Chemokines play a fundamental role in RA which occurs either through their specific receptors or through binding to the Duffy antigen receptor for chemokines (DARC) or to glycosaminoglycans (GAGs). DARC and GAGs are present on the endothelium of postcapillary venules which makes them ideally situated for being involved in the endothelial transcytosis and presentation of chemokines to leucocytes within the circulation. DARC has been shown to be involved in inflammation. This study has shown that DARC expression is present on the endothelium in synovia of patients with early and longstanding RA Through the use of radioligand binding assays on erythrocytes and in situ binding studies in RA and non-RA synovia, it has been revealed that DARC has some selectivity in which chemokines it binds. It bound to 60% of inflammatory chemokines examined and it did not bind the constitutive chemokines, with the exception of CCL17. The binding profile on endothelial cells was also found to be the same as that on the erythrocytes. DARC was also found not to bind to ELR negative CXC chemokines with the exception ofCXCLl1. It was observed that there was a decrease in the presence of heparan sulphate on the endothelium of venules in RA synovia. It was possible to compete off CXCL8 binding to heparan sulphate using the low molecular weight heparin, Monoparin. Different sized heparin saccharides could also reduce the binding ofCXCL8, with the most effective being the 24-mer.