Plasminogen activator-specific inhibitors produced by human monocytes/macrophages.
Human monocytes/macrophages produce plasminogen activator-specific inhibitors (PAIs) that form covalent complexes with urokinase-type plasminogen activator (uPA). We have characterized two functionally and antigenically related forms of PAIs produced by resting and phorbol myristate acetate (PMA)-treated U 937 cells: an Mr 40,000 form, presumably nonglycosylated, with a pI of 5.2, that is constitutively synthetized by these cells and that remains predominantly intracellular; a PMA-induced form of heterogeneous Mr (50,000-65,000) with a pI of 4.7, that is preferentially secreted; this PAI is glycosylated with terminal sialic acid residue(s). Biosynthetic labeling experiments demonstrated that both PAIs are synthetized by U 937 cells. They are inactivated upon treatment with propanol, heat, and acid; the covalent and equimolar complexes formed between these PAIs and 125I-uPA are dissociated by ammonium hydroxide, suggesting that the PAIs are linked to uPA via an ester bond. Human peripheral blood monocytes/macrophages also produce the two forms of PAI. These PAIs are clearly different from the main plasma protease inhibitors and they are both antigenically related to the PAI-2 characterized in human placenta.
D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes / Q000276:immunology; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D006031:Glycosylation; D006644:Histiocytes; D006801:Humans; D007700:Kinetics; D008223:Lymphoma; D008264:Macrophages / Q000378:metabolism*; D008970:Molecular Weight; D009000:Monocytes / Q000378:metabolism*; D010920:Placenta / Q000032:analysis; D010960:Plasminogen Activators / Q000378:metabolism; D015849:Plasminogen Inactivators; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D000939:Epitopes; D006023:Glycoproteins; D015849:Plasminogen Inactivators; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate