Binding of plasminogen to extracellular matrix. J Biol Chem 1986 Aug 15;261(23):10765-71
Date
08/15/1986Pubmed ID
3090040Scopus ID
2-s2.0-0022969199 (requires institutional sign-in at Scopus site) 148 CitationsAbstract
We have previously demonstrated that plasminogen immobilized on various surfaces forms a substrate for efficient conversion to plasmin by tissue plasminogen activator (t-PA) (Silverstein, R. L., Nachman, R. L., Leung, L. L. K., and Harpel, R. C. (1985) J. Biol. Chem. 260, 10346-10352). We now report the binding of human plasminogen to the extracellular matrix synthesized in vitro by cultured endothelial cell monolayers. The binding was specific, saturable at plasma plasminogen concentrations, reversible, and lysine-binding site-dependent. Functional studies demonstrated that matrix immobilized plasminogen was a much better substrate for t-PA than was fluid phase plasminogen as shown by a 100-fold decrease in Km. Activation of plasminogen by t-PA and urokinase on the matrix was equally efficient. The plasmin generated on the matrix, in marked contrast to fluid phase, was protected from its fast-acting inhibitor, alpha 2-plasmin inhibitor. Matrix-associated plasmin converted bound Glu- into Lys-plasminogen, which in turn is more rapidly activated to plasmin by t-PA. The extracellular matrix not only binds and localizes plasminogen but also improves plasminogen activation kinetics and prolongs plasmin activity in the subendothelial microenvironment.
Author List
Knudsen BS, Silverstein RL, Leung LL, Harpel PC, Nachman RLAuthor
Roy L. Silverstein MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Cells, CulturedEndothelium
Extracellular Matrix
Female
Humans
Muscle, Smooth, Vascular
Plasminogen
Pregnancy
Protein Binding
Tissue Plasminogen Activator
Umbilical Veins