RA is a destructive and chronic autoimmune inflammatory disease. The inflammation of the synovium is associated with the local invasion of inflammatory cells across blood vessel endothelial cells (ECs), increases in synovial fluid volume and local pannus invasion of the connective tissues and bone. Synovial ECs in RA are involved in a wide range of processes, and chemokines are known mediators of inflammatory cell invasion into the tissue. Chemokines at the ECs of lymph vessels play a further role in attracting the infiltrates out of the tissue. This study used immunofluorescence to investigate the presentation of a number chemokines in RA tissue ECs, and also the presentation of CCL7, CCL14, CCL16 and CCL22 in lymphatic ECs. A number of chemokines were newly identified in synovial ECs, and continued investigation showed a marked dysregulation in blood vessel and lymphatic vessel chemokine presentation, including CCL7. In vitro studies showed that the chemokines also preferentially generated microvilli which may facilitate transendothelial migration in vivo. Mononuclear cells expressed the receptors for the chemokines and transmigration analysis showed CCL7 (among others) to significantly chemoattract monocytes. This suggests that dysregulation of chemokines may have a functional role in RA pathology. Furthermore, the analysis of these chemokines in matched synovial fluid (DF) and serum indicates that EC chemokines may be inflammatory markers in arthritic diseases. Overall, this study has shown that the EC interface between the influx and efflux of inflammatory cells in the RA synovium may offer currently unexplored therapeutic opportunities.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:695607 |
| Date | January 2016 |
| Creators | Rump-Goodrich, Lisa |
| Publisher | Keele University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://eprints.keele.ac.uk/2355/ |
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