Galectin-3 is induced in rheumatoid arthritis synovial fibroblasts after adhesion to cartilage oligomeric matrix protein.
BACKGROUND
Galectin-3 is expressed in the synovial tissue of patients with rheumatoid arthritis (RA), particularly at sites of joint destruction.


OBJECTIVE
To explore the possibilities that galectin-3 is induced either by proinflammatory cytokines or by adhesion to cartilage components.


METHODS
Cell culture plates were coated with fibronectin, collagens I-VI, or cartilage oligomeric matrix protein (COMP), and the suspended cells were then added. The medium was changed after 1 hour at 37 degrees C. Adherent cells were further incubated for 18 hours in the presence or absence of tumour necrosis factor alpha (TNF alpha) or interleukin 1 beta. Cells were pretreated with murine IgG1, anti-CD29, -CD51, -CD61 (integrins), or -CD3 monoclonal antibodies and transferred to culture plates coated with COMP. Adherent cells were counted by light microscopy. The expression of intracellular galectin-3, or cell surface CD29, CD51, and CD61 was determined by flow cytometry before and after adhesion.


RESULTS
Four times more RA synovial fibroblasts (SF) than osteoarthritis SF adhered to COMP. RA SF presented more cell surface integrins, and monoclonal antibodies against CD51 inhibited the adhesion to COMP by 80%. TNF alpha reduced the expression of CD61 and the adhesion to COMP, but did not reverse the adhesion once it had taken place. The adhesion of RA SF to COMP was found to increase the intracellular level of galectin-3. In contrast, intracellular galectin-3 decreased after exposure to TNF alpha.


CONCLUSIONS
The increase of galectin-3 occurs after adhesion to COMP, and the alpha V beta 3 receptor (CD51/CD61) has a pivotal role in this process.
Neidhart
M
M
Centre for Experimental Rheumatology, University Hospital, Gloriastrasse 25, CH-8091 Zurich, Switzerland. michel.neidhart@usz.ch
Zaucke
F
F
von Knoch
R
R
Jüngel
A
A
Michel
B A
BA
Gay
R E
RE
Gay
S
S
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D064236:Cartilage Oligomeric Matrix Protein; D002448:Cell Adhesion; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D037502:Galectin 3 / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism; D039661:Integrin beta3 / Q000378:metabolism; D064235:Matrilin Proteins; D013583:Synovial Membrane / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D037502:Galectin 3; D006023:Glycoproteins; C061248:ITGB3 protein, human; D039564:Integrin alphaV; D039661:Integrin beta3; D064235:Matrilin Proteins; C577553:TSP5 protein, human; D014409:Tumor Necrosis Factor-alpha