Title:
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A study of endothelial chemokine binding sites in the rheumatoid synovium
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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.
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