High affinity glycosaminoglycan and autoantigen interaction explains joint specificity in a mouse model of rheumatoid arthritis. J Biol Chem 2009 Jan 23;284(4):2354-62
Date
10/25/2008Pubmed ID
18948258Pubmed Central ID
PMC2629098DOI
10.1074/jbc.M806458200Scopus ID
2-s2.0-59049108108 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
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.
Author List
Studelska DR, Mandik-Nayak L, Zhou X, Pan J, Weiser P, McDowell LM, Lu H, Liapis H, Allen PM, Shih FF, Zhang LMESH terms used to index this publication - Major topics in bold
AnimalsArthritis, Rheumatoid
Autoantigens
Biocatalysis
Cartilage
Disaccharides
Disease Models, Animal
Glucose-6-Phosphate Isomerase
Glycosaminoglycans
Mice
Mice, Inbred BALB C
Molecular Structure
Protein Binding
Substrate Specificity
