, Volume 22, Issue 3, pp 287–305 | Cite as

Binding of Latent Matrix Metalloproteinase 9 to Fibrin: Activation via a Plasmin-Dependent Pathway

  • Gregory S. Makowski
  • Melinda L. Ramsby


The binding of two matrix metalloproteinases (MMP) to fibrin was evaluated. MMP-2 (72-kDa) and MMP-9 (92-, 130-, and 225-kDa) were selected since both contain a fibronectin-like region and fibronectin binds fibrin. 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 sigmoidal binding profiles whereas 92-kDa uptake was hyperbolic. Fibronectin and TIMP-1 competition studies indicated that the fibronectin and C-terminal MMP-9 domains, respectively, were not involved with fibrin binding. 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 proteolytic activation. This process was inhibited by ∈-aminocaproic acid, indicating a plasmin-dependent pathway. The significance of these findings to procoagulant activity and MMP-mediated extracellular matrix destruction during inflammation and tumor invasion and metastasis is discussed.


Gelatin Proteolytic Activation Gelatin Zymography Membrane Collagen Binding Profile 
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Copyright information

© Plenum Publishing Corporation 1998

Authors and Affiliations

  • Gregory S. Makowski
    • 1
  • Melinda L. Ramsby
    • 2
  1. 1.Department of Laboratory MedicineUniversity of Connecticut Health CenterFarmington
  2. 2.Department of Medicine, School of MedicineUniversity of Connecticut Health CenterFarmington

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