Background and Objectives CD55 (decay-accelerating factor) is a complement-regulating protein, expressed at unusually large amounts by fibroblast-like synoviocytes (FLS) in the intimal lining in rheumatoid arthritis (RA). CD55 is also a ligand for CD97, an adhesion-type G protein-coupled receptor, broadly expressed by immune cells invading the inflamed synovium. We previously reported a protective effect of lack of CD55 in experimental models of RA (Hoek et al, Arthritis Rheum 2010; 62(4): 1036–42). Current data cannot explain the high expression of CD55 by FLS. Therefore, we explored in detail the pattern of CD55 expression in RA synovial tissue and 3-D organ cultures.
Materials and Methods Synovial tissue was obtained by miniarthroscopy and analysed by immunohistochemistry staining to visualise CD55 and collagen type III, a constituent of extracellular matrix. Reticular fibres were visualised with Gomori silver staining. Expression of CD55 mRNA in synovial tissue was detected using antisense locked nucleic acid (LNA) oligomers. CD55 expression on 2-D-cultured RA-FLS and on blood cells of healthy individuals was detected by flow cytometry and related to mRNA levels measured by qPCR. 3-D micromasses of RA-FLS were generated in matrigel and analysed by immunohistochemistry for CD55 and reticular fibres.
Results CD55 was highly expressed in the synovial lining of RA tissue, both at the mRNA and the protein level. Notably, CD55 showed an extracellular staining pattern, which coincided with Gomori silver staining of reticular fibres on sequential sections. CD55 expression on 2D-cultured FLS was less abundant and comparable to PBMCs. In 3D-micromasses of RA-FLS, CD55 was upregulated after 3–4 weeks of culture and showed an extracellular distribution that resembled reticular fibres.
Conclusions CD55 mRNA and protein is abundantly expressed by FLS in the intimal lining of RA synovial tissue. We provide evidence that FLS-derived CD55 is deposited in extracellular matrix structures such as reticular fibres, where it may contribute to the synovial stromal address code that facilitates the recruitment of immune cells.
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