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Plasminogen activator-specific inhibitors produced by human monocytes/macrophages

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Published in Journal of Experimental Medicine. 1987, vol. 165, no. 2, p. 320-339
Abstract 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.
Keywords Cell LineElectrophoresis, Polyacrylamide GelEpitopes/immunologyGlycoproteins/antagonists & inhibitors/immunology/ metabolismGlycosylationHistiocytesHumansKineticsLymphomaMacrophages/ metabolismMolecular WeightMonocytes/ metabolismPlacenta/analysisPlasminogen Activators/metabolismPlasminogen InactivatorsTetradecanoylphorbol Acetate/pharmacologyUrokinase-Type Plasminogen Activator/metabolism
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PMID: 2434595
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WOHLWEND, Annelise Isabelle, BELIN, Dominique, VASSALLI, Jean-Dominique. Plasminogen activator-specific inhibitors produced by human monocytes/macrophages. In: Journal of Experimental Medicine, 1987, vol. 165, n° 2, p. 320-339. https://archive-ouverte.unige.ch/unige:9101

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Deposited on : 2010-07-12

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