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P106 Tissue factor pathway inhibitor (TFPI) is cleaved by multiple proteases in COPD lungs to affect circulating TFPI levels
  1. B Mallia-Milanes,
  2. H Bailey,
  3. G Meakin,
  4. A Sheehan,
  5. A Knox,
  6. C Bolton,
  7. S Johnson
  1. University of Nottingham, Nottingham, UK

Abstract

Background Tissue factor pathway inhibitor (TFPI) attenuates intravascular coagulation, a function limited by its proteolysis. Airway inflammation in COPD is associated with protease activity and intravascular thrombotic events, yet the link between proteolysis of TFPI in the airways and intravascular thrombosis in COPD is unexplored.

Aims To explore the presence and processing of TFPI in COPD airways and its relationship to plasma TFPI levels.

Methods COPD sputum and blood were collected at exacerbation and when stable. In vitro cleavage of TFPI was explored by incubation with proteases and Western blotting. TFPI presence and cleavage in sputum was detected by Western blotting. To determine the main protease/s involved in TFPI cleavage, sputum was spiked with recombinant TFPI in the presence of protease inhibitors, followed by Western blotting.

Results TFPI was cleaved in vitro by Matrix Metalloproteinase (MMP)-12, Neutrophil Elastase (NE) and urokinase-type plasminogen activator (uPA) to <20.

Conclusion TFPI is cleaved by NE in COPD airways, leading to lower circulating levels. Further studies are needed to determine if lower circulating TFPI levels lead to increased intravascular thrombotic events in COPD.

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