INFLUENCE OF ION-CHANNEL MODULATION ON IN-VITRO INTERFERON-GAMMA-INDUCED MHC CLASS-I AND CLASS-II EXPRESSION ON MACROPHAGES

The in vitro effect of K+ channel blockers quinidine and verapamil, an ion channel blocker SITS and K+ channel openers diazoxide, pinacidil, and BRL 38227 on interferon-gamma (IFN-gamma) induced MHC class I and II expression of Lewis rat peritoneal macrophages was investigated by cell ELISA assay. MHC class I expression was significantly enhanced by diazoxide at concentrations of 10(-5)M to 10(-6)M and by pinacidil an d BRL 38227 at the concentration of 10(-6)M. MHC class II expression w as enhanced by pinacidil and BRL 38227 at concentrations of 10(-5)M to 10(-6)M. The enhancing effect of pinacidil could be blocked by inhibi tors of the protein kinases PKA and PKC suggesting that activation of both is required for optimum induction of MHC molecule expression. KC and anion channel blockers were less active in modulation of MHC molec ule expression. Verapamil had no influence, quinidine suppressed MHC c lass I expression at concentrations of 10(-4)M to 10(-5)M and SITS sup pressed MHC class I expression at the concentration of 10(-3)M. Since MHC class II expression is essential for efficient antigen presentatio n to T helper cells and MHC class I expression is required for target cell lysis by cytotoxic T cells, ion channel modulating drugs may be p otential candidates for immunopharmacological intervention in inflamma tory diseases.