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Expression of matrix metalloproteinases by human plasma cells and B lymphocytes
N Di Girolamo1, N Tedla, A Lloyd
1Inflammation Research Unit, School of Pathology, The University of New South Wales, Sydney, Australia.
Abstract:
Matrix metalloproteinases (MMP) are proteolytic enzymes that play a key role in tissue remodelling during physiological and pathological processes, by initiating the degradation of extracellular matrix. MMP overexpression can lead to tissue destruction which is characteristic of chronic inflammatory diseases such as rheumatoid arthritis and scleritis. Plasma cells are often abundant at such sites of chronic inflammation. In the present study we investigated whether plasma cells could contribute to matrix degradation by their expression of MMP In situ hybridization and immunohistochemical analyses on diseased synovial and scleral tissue demonstrated the expression of stromelysin-1 (MMP-3) and gelatinase B (MMP-9), but little or no tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) mRNA, by IgG-positive plasma cells. Northern blot analysis of RNA extracted from a human plasma cell line (ARH-77), Epstein-Barr virus-transformed B cells, and purified peripheral blood B cells, demonstrated expression of stromelysin mRNA. TIMP-1 mRNA was only detected by the more sensitive reverse transcription PCR method in these cell types. Plasma cells and B lymphocytes cultured in the presence of monensin demonstrated cytoplasmic gelatinase B. Gelatin and casein zymography on conditioned media (CM) derived from cytokine treated plasma cells revealed the induction of secreted gelatinase and stromelysin activity. Western blotting confirmed the presence of stromelysin-1 and TIMP-1 proteins in plasma cell CM. These data suggest that plasma cells are not only capable of modulating an inflammatory response by antibody and cytokine production, but also by their ability to produce MMP. Secretion of MMP from focal aggregates of plasma cells may play a critical role in tissue destructive diseases such as rheumatoid synovitis and scleritis.
Insights
Plasma cells, abundant in chronic inflammation, can produce matrix metalloproteinases (MMPs). These enzymes, like MMP-3 and MMP-9, contribute to tissue degradation in diseases such as rheumatoid arthritis.
Area of Science:
- Immunology
- Biochemistry
- Cell Biology
Background:
- Matrix metalloproteinases (MMPs) are crucial for tissue remodeling but their overexpression causes destruction in chronic inflammatory diseases.
- Plasma cells are common in inflamed tissues and may contribute to matrix degradation.
Purpose of the Study:
- To investigate the expression and secretion of MMPs by plasma cells.
- To determine if plasma cells contribute to tissue degradation in inflammatory conditions.
Main Methods:
- In situ hybridization and immunohistochemistry on diseased tissues.
- Northern blot, RT-PCR, zymography, and Western blotting on plasma cells and B cells.
- Analysis of plasma cell-conditioned media.
Main Results:
- Plasma cells express MMP-3 and MMP-9 mRNA and proteins, with limited TIMP-1.
- Cultured plasma cells secrete active MMPs, including gelatinase and stromelysin.
- Cytokine treatment induces MMP secretion from plasma cells.
Conclusions:
- Plasma cells contribute to matrix degradation through MMP production, beyond antibody and cytokine roles.
- MMP secretion by plasma cells may be critical in destructive inflammatory diseases like rheumatoid synovitis and scleritis.