The Involvement of CD44 and Its Novel Ligand Galectin-8 in Apoptotic Regulation of Autoimmune Inflammation
Open Access
- 15 July 2007
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 179 (2), 1225-1235
- https://doi.org/10.4049/jimmunol.179.2.1225
Abstract
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 × 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.Keywords
This publication has 38 references indexed in Scilit:
- Expression of extra trinucleotide in CD44 variant of rheumatoid arthritis patients allows generation of disease-specific monoclonal antibodyJournal of Autoimmunity, 2007
- A fibrin based model for rheumatoid synovitisAnnals Of The Rheumatic Diseases, 2003
- Sustained Induction of ERK, Protein Kinase B, and p70 S6 Kinase Regulates Cell Spreading and Formation of F-actin Microspikes Upon Ligation of Integrins by Galectin-8, a Mammalian LectinOnline Journal of Public Health Informatics, 2003
- CD44 in CancerCritical Reviews in Clinical Laboratory Sciences, 2002
- The balance of Th1/Th2 cytokines in rheumatoid arthritisBest Practice & Research Clinical Rheumatology, 2001
- Tumors and FibrinogenAnnals of the New York Academy of Sciences, 2001
- CD44-related chondroitin sulfate proteoglycan, a cell surface receptor implicated with tumor cell invasion, mediates endothelial cell migration on fibrinogen and invasion into a fibrin matrix.JCI Insight, 1996
- Apoptosis of T cells mediated by galectin-1Nature, 1995
- Galectin-8Journal of Biological Chemistry, 1995
- A PCR-based method for the analysis of human CD44 splice products.Genome Research, 1993