CALPAIN EXPRESSION IN LYMPHOID-CELLS - INCREASED MESSENGER-RNA AND PROTEIN-LEVELS AFTER CELL ACTIVATION

Although calpain is ubiquitously present in human tissues and is thoug ht to play a role in demyelination, its activity is very low in restin g normal lymphocytes. To determine the nature of calpain expression at the mRNA and protein levels in human lymphoid cells, we studied human T lymphocytic, B lymphocytic, and monocytic Lines as well as peripher al blood mononuclear cells. Stimulation of cells with the phorbol este r phorbol myristate acetate and the calcium ionophore A23187 resulted in increased calpain mRNA and protein expression. Calpain mRNA express ion is also increased in human T cells stimulated with anti-CD3. A dis sociation between the increases of RNA and protein suggested that calp ain could be released from the cells; the subsequent experiments showe d its presence in the extracellular environment, 5,6-Dichloro-1b-D-rib ofuranosylbenzimidazoIe, a reversible inhibitor of mRNA synthesis, red uced calpain mRNA levels by 50-67% and protein levels by 72-91%, Its r emoval resulted in resumption of both calpain mRNA and protein synthes is. Cycloheximide, a translational inhibitor, reduced calpain protein levels by 77-81% and calpain mRNA levels by 96% in activated THP-1 cel ls. Interferon-gamma induced calpain mRNA and protein in U-937 and THP -1 cells. Dexamethasone increased mRNA expression in THP-1 cells, Our results indicate that activation of lymphoid cells results in de novo synthesis and secretion of calpain.