title: FDP D-dimer induces the secretion of interleukin-1, urokinase-type plasminogen activator, and plasminogen activator inhibitor-2 in a human promonocytic leukemia cell line.
abstract: We studied the effect of fibrinogen degradation products D, E, and D-dimer on a human promonocytic leukemia cell line, NOMO-1. After exposure to a 10(-5)-mol/L fragment D or D-dimer, the cells displayed macrophage-like characteristics, such as adherence to plastic surfaces, and showed approximately a twofold increase in response to the nitroblue tetrazolium reduction test. The secretion of interleukin-1 alpha (IL-1 alpha) into the medium was markedly stimulated by a 10(-5)-mol/L fragment D, E, and D-dimer, whereas a significant increase in IL-1 beta secretion was observed only in D-dimer-stimulated cells. In addition, D-dimer induced a rapid increase in urokinase-type plasminogen activator on day 1 (0.52 +/- 0.02 ng/mL v 0.07 +/- 0.01 ng/mL in the control culture) and a slow increase in plasminogen activator inhibitor-2 on day 5 (3.9 +/- 1.6 ng/mL v 1.2 +/- 0.2 ng/mL in the control culture). An increase in tissue factor (TF) was also demonstrated on the cell surface of NOMO-1 cells exposed to fragment D or D-dimer by indirect immunofluorescence using an anti-TF monoclonal antibody. Scatchard plot analysis showed that fragment D and D-dimer bound to the NOMO-1 cells with a kd of 3.3 nmol/L and 2.7 nmol/L, respectively. These results suggest that fragment D-dimer specifically stimulates cells of monocyte-macrophage lineage to secrete key substances that regulate blood coagulation, fibrinolysis, and inflammation.
authors.affiliation: First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Morishita
authors.forename: I
authors.initials: I
authors.lastname: Takahashi
authors.forename: M
authors.initials: M
authors.lastname: Ogura
authors.forename: J
authors.initials: J
authors.lastname: Takamatsu
authors.forename: H
authors.initials: H
authors.lastname: Saito
mesh_terms: D000911:Antibodies, Monoclonal; D002460:Cell Line; D004792:Enzyme Precursors / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000378:metabolism*; D007700:Kinetics; D007938:Leukemia; D010587:Phagocytosis / Q000187:drug effects; D010960:Plasminogen Activators / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D004792:Enzyme Precursors; D005338:Fibrin Fibrinogen Degradation Products; D007375:Interleukin-1; D015849:Plasminogen Inactivators; D013481:Superoxides; D013925:Thromboplastin; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator