Proteolysis of the endothelial cell protein C receptor by neutrophil proteinase 3
2007

How Neutrophil Proteinase 3 Affects Endothelial Cell Protein C Receptor

publication Evidence: high

Author Information

Author(s): VILLEGAS-MENDEZ A, MONTES R, AMBROSE L R, WARRENS A N, LAFFAN M, LANE D A

Primary Institution: Imperial College London

Hypothesis

Activated neutrophils can proteolytically cleave the endothelial cell protein C receptor (EPCR).

Conclusion

The study shows that proteinase 3 from activated neutrophils binds to and cleaves EPCR, potentially down-regulating anticoagulant pathways during inflammation.

Supporting Evidence

  • Activated neutrophils decrease EPCR expression on endothelial cells over time.
  • PR3 cleaves EPCR at multiple sites, leading to its degradation.
  • Binding studies indicate a high affinity interaction between PR3 and EPCR.

Takeaway

When certain white blood cells called neutrophils get activated, they can chop up a protein that helps prevent blood clots, which might make inflammation worse.

Methodology

The study involved isolating human neutrophils and examining their interaction with endothelial cells and the soluble form of EPCR using flow cytometry and various biochemical assays.

Limitations

The study primarily focuses on in vitro experiments, which may not fully replicate in vivo conditions.

Participant Demographics

Human neutrophils were isolated from healthy donors.

Digital Object Identifier (DOI)

10.1111/j.1538-7836.2007.02480.x

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication