Beta Integrins (α4β1, α5β1) and Matrix Metalloproteinases Expression in Synovial Pannus Formation in Rheumatoid Arthritis

概要

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To investigate the mechanism of synovial pannus formation in rheumatoid arthritis, immunohisochemical studies with monoclonal antidodies against the adhesion molecules, α4β1, α5β1 integrins and matrix metalloproteinases (MMP-1, MMP-3) and tissue inhibitor of metalloproteinase (TIMP-1), were carried out to determine the pattern of the distribution of these molecules at the rheumatoid synovial carilage junction. Treatment with purified anti-human monoclonal anti-bodies, anti-α4β1 and α5β1, resulted in membrane staining of most of the cells infiltrating the synovial tissue and bordering the pannus cartilage junction. The α4β1 and α5β1 interaction appeared to be involved in the attachment of the pannus. Staining for MMP-1 and MMP-3 was particularly intense at the pannus-cartilage junction. These molecules were also strongly stained in the cartilage matrix bordering the tip of pannus invasion. TIMP-1 staining disclosed very weak cellular staining and weak extracellular staining at the pannus-cartilage junction. The present study indicates that a receptor-ligand interaction between β1 integrin and cartilage matrix may occur at the early stage of pannus formation, and that this is followed by elevated proteolytic activity of MMPs and a decreased level of TIMP-1. And in this way, these changes may contribute to pannus invasion and cartilage destruction.
神戸大学の論文
2000-12-27