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Inflammation

, 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
Article

Abstract

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.

Keywords

Gelatin Proteolytic Activation Gelatin Zymography Membrane Collagen Binding Profile 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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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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