PLASMINOGEN ACTIVATION STIMULATES AN INCREASE IN INTRACELLULAR CALCIUM IN HUMAN SYNOVIAL FIBROBLASTS

Both plasminogen (Pg) and urinary-type Pg activator (u-PA), but not ti ssue-type Pg activator (t-PA), bind to normal and rheumatoid arthritis (RA) human synovial fibroblasts in culture with high affinity and in a dose-dependent manner. Single cell intracellular Ca2+ responses to P g and u-PA were studied using Fura-2 and digital imaging fluorescence microscopy. Pg activation by u-PA on the surface of RA synovial fibrob lasts induces a significant rise in cytosolic free Ca2+ concentration ([Ca2+]i) within 90 s. Pg kringle 4 and the alpha2,3-linked sialic aci d in the carbohydrate chain bound to Thr245 are involved in mediating the increases in [Ca2+)i. This response is not observed in normal syno vial fibroblasts, suggesting that RA synovial fibroblasts have altered responses to the binding and activation of Pg on their surfaces.