BINDING OF LATENT MATRIX METALLOPROTEINASE 9 TO FIBRIN - ACTIVATION VIA A PLASMIN-DEPENDENT PATHWAY

The binding of two matrix metalloproteinases (MMP) to fibrin was evalu ated. MMP-2 (72-kDa) and MMP-9 (92-, 130-, and 225-kDa) were selected since both contain a fibronectin-like region and fibronectin binds fib rin. Gelatin zymography indicated selective and dose dependent binding of MMP-9 to fibrin. No MMP-2 binding to fibrin occurred. Densitometry revealed that the 130- and 225-kDa forms demonstrated similar sigmoid al binding profiles whereas 92-kDa uptake was hyperbolic. Fibronectin and TIMP-1 competition studies indicated that the fibronectin and C-te rminal MMP-9 domains, respectively, were not involved with fibrin bind ing. The MMP-9 collagen-like region may be of regulatory significance since type I and II fibrillar and type Iv basement membrane collagens demonstrated fibrin binding. During fibrinolysis, latent fibrin-bound MMP-9 was processed to lower molecular weight forms consistent with pr oteolytic activation. This process was inhibited by E-aminocaproic aci d, indicating a plasmin-dependent pathway. The significance of these f indings to procoagulant activity and MMP-mediated extracellular matrix destruction during inflammation and tumor invasion and metastasis is discussed.