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Immunolocalization of matrix metalloproteinase 3 (stromelysin) in rheumatoid synovioblasts (B cells): correlation
Y Okada1, N Takeuchi, K Tomita
1Department of Pathology, School of Medicine, Kanazawa University, Ishikawa, Japan.
Abstract:
Metalloproteinases produced by connective tissue cells may play a key part in the destruction of joints in rheumatoid arthritis. Matrix metalloproteinase 3 (MMP-3; stromelysin) capable of degrading cartilage proteoglycans and type IX collagen and of activating procollagenase was immunolocalised in hyperplastic synovial lining cells in rheumatoid synovium, but not in the cells of normal synovium. Cells responsible for synthesis of MMP-3 have the phenotype of synovioblasts (B cells) by immunoelectron microscopy, but not of phagocytic synovial macrophages (A cells). Cultured monolayer of rheumatoid synovial cells synthesises MMP-3 only under treatment with macrophage conditioned medium. Immunolocalisation of MMP-3 in rheumatoid synovium and cultured synovial cells was possible when the specimens were treated with a monovalent ionophore, monensin. These results suggest that MMP-3 is synthesised and secreted continuously without storage from hyperplastic synovioblasts stimulated by factor(s) derived from activated macrophages present in the synovium.
Insights
Matrix metalloproteinase 3 (MMP-3) is found in rheumatoid arthritis synovium, produced by synovioblasts stimulated by macrophages. This enzyme degrades joint cartilage, contributing to disease progression.
Area of Science:
- Biochemistry
- Immunology
- Rheumatology
Background:
- Connective tissue metalloproteinases contribute to joint destruction in rheumatoid arthritis.
- Matrix metalloproteinase 3 (MMP-3), also known as stromelysin, degrades cartilage proteoglycans and type IX collagen.
- MMP-3 can also activate procollagenase, further contributing to tissue breakdown.
Purpose of the Study:
- To immunolocalize MMP-3 in rheumatoid synovium.
- To identify the cell types responsible for MMP-3 synthesis.
- To investigate the regulation of MMP-3 synthesis in rheumatoid synovial cells.
Main Methods:
- Immunoelectron microscopy was used to localize MMP-3 in rheumatoid synovium and cultured synovial cells.
- Rheumatoid synovial cells were cultured and treated with macrophage conditioned medium.
- Specimens were treated with monensin, a monovalent ionophore, to enhance MMP-3 immunolocalization.
Main Results:
- MMP-3 was localized in hyperplastic synovial lining cells of rheumatoid synovium, but not in normal synovium.
- Cells synthesizing MMP-3 exhibited the phenotype of synovioblasts (B cells), not synovial macrophages (A cells).
- Cultured rheumatoid synovial cells synthesized MMP-3 only when treated with macrophage conditioned medium.
Conclusions:
- MMP-3 is synthesized and continuously secreted without storage by hyperplastic synovioblasts.
- Activated macrophages in the synovium likely provide factors that stimulate MMP-3 synthesis by synovioblasts.
- These findings highlight the role of MMP-3 in rheumatoid arthritis pathogenesis.