Comparison of plasminogen binding and activation on extracellular matrices produced by vascular smooth muscle and endothelial cells.
Plasminogen is the zymogen form of the serine proteinase plasmin. Although plasmin functions primarily as a fibrinolytic enzyme, recent evidence from numerous laboratories indicates that plasmin is also active in extracellular-matrix (ECM) proteolysis. The role of plasmin in ECM degradation suggests that activation of plasminogen may be regulated by interaction with components of the ECM. In the current study, we have investigated binding and kinetic interactions between plasminogen, plasminogen activators and ECM synthesized by either vascular smooth muscle cells (SMCECM) or endothelial cells (ECECM). We report binding of plasminogen, tissue-type plasminogen activator (t-PA) and urinary-type plasminogen activator (u-PA) to intact SMCECM with concentrations of ligand yielding half-maximal binding (B50) of 34, 5 and 15 nM, respectively. ECECM bound only plasminogen and t-PA, with B50 values of 32 nM and 10 nM, respectively. The initial rate of t-PA-catalyzed plasminogen activation was enhanced 41-fold in the presence of SMCECM and 27-fold on ECECM. In contrast, u-PA-catalyzed activation on SMCECM and ECECM was increased only 1.5-fold or 3-fold, respectively. These data suggest that the ECM may provide an alternative surface for assembly and regulation of plasminogen activation.
Stack
M S
MS
Department of Obstetrics and Gynecology, Northwestern University Medical School, Chicago, IL 60611.
Rinehart
A R
AR
Pizzo
S V
SV
D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta; D004730:Endothelium, Vascular / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D051381:Rats; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014471:Umbilical Veins; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator