An immunohistochemical and immunoelectron microscopic study of beta integrins (α4β1, α5β1) and matrix metalloproteinases expression in rheumatoid synovial pannus formation in rheumatoid arthritis

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To investigate the mechanism of synovial pannus formation in rheumatoid arthritis, immunohisochemical and immunoelectron microscopic studies with monoclonal antibodies against the adhesion molecules, α4β1, α5β1 integrins and matrix metalloproteinases (MMP-1, MMP-3) and tissue inhibitor of metallo-proteinase (TIMP-1), were carried out to determine the pattern of the distribution of these molecules at the rheumatoid synovial cartilage junction. Treatment with purified anti-human monoclonal antibodies, 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. The VLA-5 molecule was found in a pericellular and interterritorial matrix distribution in the present study. 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 contributing to pannus invasion and cartilage destruction.
神戸大学の論文
2001-11-30

An immunohistochemical and immunoelectron microscopic study of beta integrins (α4β1, α5β1) and matrix metalloproteinases expression in rheumatoid synovial pannus formation in rheumatoid arthritis

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