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THU0106 The expression of ip-10 and mig chemokines in rheumatoid synovial tissue
  1. J Niederlova1,
  2. J Vencovsky1,
  3. O Krystufkova1,
  4. D Veigl2,
  5. S Ruzickova1
  1. 1Department of Immunology, Institute of Rheumatology, Prague, Czech Republic
  2. 21st Department of Orthopaedics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic

Abstract

Objectives Rheumatoid arthritis (RA) is characterised by chronic synovial inflammation, which results in progressive polyarticular destruction. Immunohistological characterisation of infiltrating cells may help to elucidate the role of specific chemokines and their receptors in pathological processes. In this regard we previously described high expression of chemokine receptor CXCR-3 in synovial tissue. Now we have investigated expression of chemotactic factors IP-10 and Mig, which are ligands for CXCR-3.

Methods Synovial tissue samples were obtained from 5 RA patients who have undergone total joint replacement or synovectomy. Native cryostat tissue sections were examined for CD3, CD4, CD8, CD19, CD14, CD31, CD68, CXCR-3, IP-10 and Mig with mouse anti-human monoclonal antibodies. Two-step visualisation with DAKO EnVision was applied. This visualisation system is based on enzyme-conjugated dextrane polymer, which carriers secondary antibody molecules. Negative controls were performed by using izotype-matched irrelevant antibodies.

Results A strong positive reaction for CXCR-3 was detected on lymphocytes and macrophage-like synoviocytes; weak and irregular staining was seen in endothelial cells. IP-10 and Mig were expressed in all tissue samples. The positivity was found mainly in the lymphoid infiltrating cells and the staining also co-localised with CD68 positive synoviocytes. In addition, a stronger expression of IP-10 than of Mig was seen, particularly in tissues with a strong vascularity. Endothelial cells were strongly positive for IP-10 and weakly also for Mig. In general, IP-10 and Mig staining was observed in sporadic aggregates surrounding blood vessels.

Conclusion High expression of IP-10 and Mig on a majority of the infiltrating cells suggests a role for interferon-g in RA inflammation, as IP-10 and Mig are induced by this cytokine. They may play a role in the attraction of CD4 positive T cells into the synovial environment. Furthermore, a frequent expression of CXCR3 on synovial resident cells propounds a possible role for IP-10 and Mig in their activation, perhaps even in the autocrine fashion. This work was supported by a grant NI/6459 from IGA MZ CR.

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