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High affinity glycosaminoglycan and autoantigen interaction explains joint specificity in a mouse model of rheumatoid arthritis.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2009 Jan 23; Vol. 284 (4), pp. 2354-62. Date of Electronic Publication: 2008 Oct 22. - Publication Year :
- 2009
-
Abstract
- In the K/BxN mouse model of rheumatoid arthritis, autoantibodies specific for glucose-6-phosphate isomerase (GPI) can transfer joint-specific inflammation to most strains of normal mice. Binding of GPI and autoantibody to the joint surface is a prerequisite for joint-specific inflammation. However, how GPI localizes to the joint remains unclear. We show that glycosaminoglycans (GAGs) are the high affinity (83 nm) joint receptors for GPI. The binding affinity and structural differences between mouse paw/ankle GAGs and elbows/knee GAGs correlated with the distal to proximal disease severity in these joints. We found that cartilage surface GPI binding was greatly reduced by either chondroitinase ABC or beta-glucuronidase treatment. We also identified several inhibitors that inhibit both GPI/GAG interaction and GPI enzymatic activities, which suggests that the GPI GAG-binding domain overlaps with the active site of GPI enzyme. Our studies raise the possibility that GAGs are the receptors for other autoantigens involved in joint-specific inflammatory responses.
- Subjects :
- Animals
Arthritis, Rheumatoid pathology
Biocatalysis
Cartilage metabolism
Disaccharides metabolism
Disease Models, Animal
Glucose-6-Phosphate Isomerase metabolism
Glycosaminoglycans chemistry
Mice
Mice, Inbred BALB C
Molecular Structure
Protein Binding
Substrate Specificity
Arthritis, Rheumatoid immunology
Arthritis, Rheumatoid metabolism
Autoantigens immunology
Glycosaminoglycans metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 284
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 18948258
- Full Text :
- https://doi.org/10.1074/jbc.M806458200