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* Lautenberg Center for General and Tumor Immunology, and
Rheumatology Unit, Hebrew University-Hadassah Medical School, Jerusalem, Israel;
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel; and
Department of Rheumatology, Tel Aviv Souraski Medical Center, Ichilov Hospital, Sackler Faculty of Medicine, Tel Aviv, Israel
The synovial fluid (SF) cells of rheumatoid arthritis (RA) patients express a specific CD44 variant designated CD44vRA. Using a cellular model of this autoimmune disease, we show in this study that the mammalian lectin, galectin-8 (gal-8), is a novel high-affinity ligand of CD44vRA. By affinity chromatography, flow cytometry, and surface plasmon resonance, we demonstrate that gal-8 interacts with a high affinity (Kd, 6 x 10–9 M) with CD44vRA. We further demonstrate that SF cells from RA patients express and secrete gal-8, to a concentration of 25–65 nM, well within the concentration of gal-8 required to induce apoptosis of SF cells. We further show that not all gal-8 remains freely soluble in the SF and at least part forms triple complexes with CD44 and fibrinogen that can be detected, after fibrinogen immunoprecipitation, with Abs against fibrinogen, gal-8 and CD44. These triple complexes may therefore increase the inflammatory reaction by sequestering the soluble gal-8, thereby reducing its ability to induce apoptosis in the inflammatory cells. Our findings not only shed light on the receptor-ligand relationships between CD44 and gal-8, but also underline the biological significance of these interactions, which may affect the extent of the autoimmune inflammatory response in the SF of RA patients.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Concern Foundation (Los Angeles, CA), Foundation for Research into Disease of Aging (Bala Cynwyd, PA), and Women Health Research Center (Weizmann Institute).
2 Address correspondence and reprint requests to Dr. David Naor, Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel. E-mail address: naord{at}md.huji.ac.il
3 Abbreviations used in this paper: SF, synovial fluid; RA, rheumatoid arthritis; FGF, fibroblast growth factor; gal-8, galectin-8; CD44v, CD44 variant; CD44s, CD44 standard; h, human; LS, lactosyl sepharose; TDG, thiodigalactoside; PKB, protein kinase B; RU, resonance unit.
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