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THU0113 Expression of galectin-3 in rheumatoid arthritis synovium
  1. S Kuchen1,
  2. CA Seemayer1,
  3. P Kuenzler1,
  4. RE Gay1,
  5. ME Billingham2,
  6. BA Michel1,
  7. S Gay1,
  8. M Neidhart1
  1. 1Center of Experimental Rheumatology, Department Rheumatology, University Hospital, Zürich, Switzerland
  2. 2Veterinary School, University of Bristol, Bristol, UK

Abstract

Background Galectin-3 is a beta-galactoside-binding protein and belongs to the large family of lectins, which play important roles in a variety of physiological and pathophysiological processes via their recognition of glycoconjugates. Galectin-3 is involved in the regulation of cell growth and apoptosis, cell aggregation/adhesion and differentiation and is associated with cell transformation and metastasis in several tumours. Since it activates inflammatory cells by promoting cell-cell and cell-matrix interactions and acts as a chemoattractant on monocytes and macrophages, galectin-3 is suggested to play a role in inflammatory diseases. So far, galectin-3 has been shown to be expressed by monocytes and macrophages but not by T- and B-lymphocytes.

Objectives Here we investigated the expression of galectin-3 in rheumatoid arthritis (RA) and osteoarthritis (OA) synovial tissues. Furthermore, we examined the expression of galectin-3 in cultured RA synovial fibroblasts (RA-SF) and OA synovial fibroblasts (OA-SF).

Methods Paraffin-embedded synovial tissue samples from RA (n = 7) and OA (n = 3) patients were analysed for expression of galectin-3 by immunohistochemistry (IHC) and/or non-radioactive in situ hybridization (ISH) using monoclonal mouse anti-galectin-3 antibodies (Affinity bioreagents, clone A3A12) and galectin-3 specific digoxigenin-labelled RNA antisense probes, respectively. Immunohistochemical staining of CD68 with monoclonal mouse anti-human macrophage CD68 antibodies (DAKO, clone PG-M1) was performed on parallel sections. Isotype specific mouse IgG and sense RNA probes were used as negative controls. Expression of galectin-3 in cultured RA-SF (n = 10) and OA-SF (n = 1) from passage 2–7 was examined by RT-PCR.

Results Galectin-3 was found to be expressed in all RA synovial tissue samples. Positive cells were detected throughout the lining and sublining layer with a predominant expression in the sublining. In contrast, CD68 was mainly expressed in the lining layer. Endothelial cells of small vessels in the sublining were mostly positive for galectin-3, whereas endothelial cells of larger vessels were negative. Clusters of galectin-3/CD68 positive cells were located around vessels. Interestingly, galectin-3 was rarely expressed at sites of bone invasion, in contrast to CD68. In OA synovial tissues, galectin-3 and CD68 were expressed by some cells in the lining layer. All cultured RA- and OA-SF were tested positive for galectin-3 mRNA by RT-PCR.

Conclusion We conclude from our data that the expression of galectin-3 in RA synovium is not restricted to monocytes and macrophages. Moreover, we suggest that galectin-3 contributes to the inflammation rather than to the destructive processes at sites of invasion.

S. Kuchen supported by the EMDO Stiftung.

C. A. Seemayer supported by DAAD and by the Theodor und Ida Herzog-Egli Stiftung.

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