Fibrinolysis: An International Journal of Fibrinolysis and Thrombolysis vol:12 issue:1 pages:1-8
date:Catholic Univ Louvain, Ctr Mol & Vasc Biol, B-3000 Louvain, Belgium; Roswell Pk Canc Inst, Buffalo, NY USA
Specific interactions between the plasminogen/plasmin (fibrinolytic) and matrix metalloproteinase (MMP) systems suggest that both systems may cooperate in extracellular matrix degradation. Therefore, the plasminogen/ plasmin system function was evaluated in mice with stromelysin-1 (MMP-3) or tissue inhibitor of MMP type-1 (TIMP-1) gene inactivation. Urinary urokinase-type plasminogen activator (u-PA) antigen (120-190 ng/ml) and activity (13-18 IU/ml) levels were similar in both wild-type and gene-deficient mice. Vascular plasminogen activator activity, measured in aorta extracts, was similar for both tissue-type plasminogen activator (t-PA)-mediated activity (8-14 arbitrary units (AU) per mg protein) and for u-PA-mediated activity (25-34 AU per mg protein). The spontaneous thrombolytic potential (lysis of a I-125-fibrin labelled pulmonary embolus) was comparable in wild-type (MMP-3(+/+)) and MMP-3(-/-) mice (36 +/- 6% versus 49 +/- 5% after 8 h; P = 0.13), and in wild-type (TIMP-1(+/+)) and TIMP-1(-/-) mice (48 +/- 4% versus 48 +/- 2% after 8 h). Organ sections did not reveal significant fibrin deposition in the liver of any of the genotypes. Furthermore, in vivo thioglycollate-stimulated macrophages of all 4 genotypes expressed comparable u-PA-mediated plasminogen activating potential and I-125-fibrin matrix degrading potential. Thus, these data suggest that MMP-3 and TIMP-1 do not play a major role in the generation of fibrinolytic activity mediated via the plasminogen/plasmin system.