Matrix metalloproteinase deficiencies do not impair cell-associated fibrinolytic activity.
The matrix metalloproteinase (MMP) and fibrinolytic (plasminogen/plasmin) systems cooperate in many (patho)physiological processes requiring extracellular proteolysis. The effect of MMP-3 (stromelysin-1), MMP-7 (matrilysin), MMP-9 (gelatinase B) or MMP-12 (metalloelastase) on cellular fibrinolytic activity was studied with the use of smooth muscle cells (SMC) and fibroblasts derived from mice with specific inactivation of these genes. Activation of cell-bound plasminogen by two-chain urokinase-type plasminogen activator (tcu-PA) was not significantly different with SMC or fibroblasts from the gene-deficient mice (78% to 140% of wild-type). For all cell types, very limited conversion of plasminogen to angiostatin-like kringle-containing fragments was observed (< 3% of the total cell-bound plasminogen). Activation of plasminogen in solution by cell-associated tcu-PA was also comparable for SMC or fibroblasts of the different genotypes (54% to 160% of wild-type). In vitro SMC migration on scrape wounded collagen-coated surfaces was comparable for wild-type, MMP-7(-/-), MMP-9(-/-) and MMP-12(-/-) SMC, but was significantly reduced for MMP-3(-/-) SMC (P < .005 vs. wild-type). Serum-free conditioned medium of MMP-3(-/-) and MMP-7(-/-) SMC or fibroblasts induced similar lysis of fibrin films as wild-type cells. These findings indicate that several interactions that have been described between these MMPs and the plasminogen/plasmin system in a purified system do not significantly affect plasmin-mediated cellular fibrinolytic activity under cell culture conditions.
Ugwu
F
F
Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, O&N, Herestraat 49, B-3000, Leuven, Belgium.
Lemmens
G
G
Collen
D
D
Lijnen
H R
HR
D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D005342:Fibrinolysis / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000166:cytology; D010958:Plasminogen / Q000187:drug effects / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology; D014947:Wounds and Injuries / Q000473:pathology
D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases