title: Plasminogen activation stimulates an increase in intracellular calcium in human synovial fibroblasts.
abstract: 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.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: M
authors.initials: M
authors.lastname: Gonzalez-Gronow
authors.forename: G
authors.initials: G
authors.lastname: Gawdi
authors.forename: S V
authors.initials: SV
authors.lastname: Pizzo
mesh_terms: D001172:Arthritis, Rheumatoid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D010958:Plasminogen; D010960:Plasminogen Activators; D002118:Calcium