Plasminogen activation stimulates an increase in intracellular calcium in human synovial fibroblasts.

Both plasminogen (Pg) and urinary-type Pg activator (u-PA), but not tissue-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 Pg and u-PA were studied using Fura-2 and digital imaging fluorescence microscopy. Pg activation by u-PA on the surface of RA synovial fibroblasts induces a significant rise in cytosolic free Ca2+ concentration ([Ca2+]i) within 90 s. Pg kringle 4 and the alpha 2,3-linked sialic acid in the carbohydrate chain bound to Thr245 are involved in mediating the increases in [Ca2+]i. This response is not observed in normal synovial fibroblasts, suggesting that RA synovial fibroblasts have altered responses to the binding and activation of Pg on their surfaces.

Duke Scholars

Author Mario Gonzalez-Gronow Pathology

Author Salvatore Vincent Pizzo Pathology