EXPRESSION OF MATRIX METALLOPROTEINASES BY HUMAN PLASMA-CELLS AND B-LYMPHOCYTES

Matrix metalloproteinases (MMP) are proteolytic enzymes that play a ke y role in tissue remodelling during physiological and pathological pro cesses, by initiating the degradation of extracellular matrix. MMP ove rexpression can lead to tissue destruction which is characteristic of chronic inflammatory diseases such as rheumatoid arthritis and sclerit is. Plasma cells are often abundant at such sites of chronic inflammat ion. In the present study we investigated whether plasma cells could c ontribute to matrix degradation by their expression of MMP. In situ hy bridization and immunohistochemical analyses on diseased synovial and scleral tissue demonstrated the expression of stromelysin-l (MMP-3) an d gelatinase B (MMP-9), but little or no tissue inhibitor of matrix me talloproteinase 1 (TIMP-1) mRNA, by IgG-positive plasma cells. Norther n blot analysis of RNA extracted from a human plasma cell line (ARH-77 ), Epstein-Barr virus-transformed B cells, and purified peripheral blo od B cells, demonstrated expression of stromelysin mRNA. TIMP-1 mRNA w as only detected by the more sensitive reverse transcription PCR metho d in these cell types. Plasma cells and B lymphocytes cultured in the presence of monensin demonstrated cytoplasmic gelatinase B. Gelatin an d casein zymography on conditioned media (CM) derived from cytokine tr eated plasma cells revealed the induction of secreted gelatinase and s tromelysin activity. Western blotting confirmed the presence of strome lysin-1 and TIMP-1 proteins in plasma cell CM. These data suggest that plasma cells are not only capable of modulating an inflammatory respo nse by antibody and cytokine production, but also by their ability to produce MMP. Secretion of MMP from focal aggregates of plasma cells ma y play a critical role in tissue destructive diseases such as rheumato id synovitis and scleritis.