Plasma samples of 189 healthy subjects were investigated for antigen levels of the recently reported factor VII- and single-chain plasminogen activator-activating protease (FSAP) and the corresponding pro-urokinase activating potencies. While the age of donors had no significant effect on the investigated parameters, female plasmas revealed a trend to higher antigen contents and activity levels. Surprisingly, as much as 9% of all samples contained significantly reduced single-chain urinary plasminogen activator activating potential, whereas antigen concentrations were normal. Additionally, 1% of the plasmas was found to decrease in both FSAP antigen and activity contents. FSAP of three subjects displaying reduced activities throughout a follow-up period of 6 months were purified from plasmas and were characterized. As compared with pool plasma derived FSAP, investigation of the individual preparations confirmed their reduced potency to activate pro-urokinase. However, factor VII activation was not affected. It is speculated that the FSAP binding site for single-chain plasminogen activators is affected, potentially by as yet unknown polymorphism(s) or mutation(s).
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http://dx.doi.org/10.1097/00001721-200107000-00007 | DOI Listing |
Toxins (Basel)
August 2024
Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN 55108, USA.
EGFR-targeted therapies are efficacious, but toxicity is common and can be severe. Urokinase type plasminogen activator receptor (uPAR)-targeted drugs are only emerging, so neither their efficacy nor toxicity is fully established. Recombinant eBAT was created by combining cytokines EGF and uPA on the same single-chain molecule with truncated toxin.
View Article and Find Full Text PDFInt J Mol Sci
August 2024
Department of Cellular and Molecular Biology, School of Medicine, The University of Texas Health Science Center at Tyler, 11937 US HWY 271, Tyler, TX 75708, USA.
Blood Adv
July 2024
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA.
Fibrinolytics delivered into the general circulation lack selectivity for nascent thrombi, reducing efficacy and increasing the risk of bleeding. Urokinase-type plasminogen activator (uPA) transgenically expressed within murine platelets provided targeted thromboprophylaxis without causing bleeding but is not clinically feasible. Recent advances in generating megakaryocytes prompted us to develop a potentially clinically relevant means to produce "antithrombotic" platelets from CD34+ hematopoietic stem cell-derived in vitro-grown megakaryocytes.
View Article and Find Full Text PDFInt Immunopharmacol
February 2024
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan; International Master/Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; International Ph.D. Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan. Electronic address:
Unlabelled: Our prior finding that uPA endogenously expressed and stored in the platelets of transgenic mice prevented thrombus formation without causing bleeding, prompted us to develop a potentially clinically relevant means of generating anti-thrombotic human platelets from CD34 hematopoietic cell-derived megakaryocytes. CD34 -megakaryocytes internalize and store in α-granules single-chain uPA (scuPA) and a uPA variant modified to be plasmin-resistant, but thrombin-activatable, (uPAT). Both uPAs co-localized with internalized factor V (FV), fibrinogen and plasminogen, low-density lipoprotein receptor-related protein 1 (LRP1), and interferon-induced transmembrane protein 3 (IFITM3), but not with endogenous von Willebrand factor (VWF).
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