Skip to Main content Skip to Navigation
Journal articles

The Proteolytic Inactivation of Protein Z-Dependent Protease Inhibitor by Neutrophil Elastase Might Promote the Procoagulant Activity of Neutrophil Extracellular Traps in Sepsis

Abstract : Septic shock is the archetypal clinical setting in which extensive crosstalk between inflammation and coagulation dysregulates the latter. The main anticoagulant systems are systematically impaired, depleted, and/or downregulated. Protein Z-dependent protease inhibitor (ZPI) is an anticoagulant serpin that not only targets coagulation factors Xa and XIa but also acts as an acute phase reactant whose plasma concentration rises in inflammatory settings. The objective of the present study was to assess the plasma ZPI antigen level in a cohort of patients suffering from septic shock with or without overt-disseminated intravascular coagulation (DIC). The plasma ZPI antigen level was approximately 2.5-fold higher in the patient group (n = 100; 38 with DIC and 62 without) than in healthy controls (n = 31). The elevation's magnitude did not appear to depend on the presence/absence of DIC. Furthermore, Western blots revealed the presence of cleaved ZPI in plasma from patients with severe sepsis, independently of the DIC status. In vitro, ZPI was proteolytically inactivated by purified neutrophil elastase (NE) and by NE on the surface of neutrophil extracellular traps (NETs). The electrophoretic pattern of ZPI after NE-catalyzed proteolysis was very similar to that resulting from the clotting process—suggesting that the cleaved ZPI observed in severe sepsis plasma is devoid of anticoagulant activity. Taken as a whole, our results (1) suggest that NE is involved in ZPI inactivation during sepsis, and (2) reveal a novel putative mechanism for the procoagulant activity of NETs in immunothrombosis.
Complete list of metadata

https://www.hal.inserm.fr/inserm-03313257
Contributor : Elsa Bianchini <>
Submitted on : Tuesday, August 3, 2021 - 4:25:28 PM
Last modification on : Saturday, August 7, 2021 - 3:48:23 AM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : 2021-12-16

Please log in to resquest access to the document

Identifiers

Citation

Elsa Bianchini, Mahita Razanakolona, Julie Helms, Fouzia Zouiti, Amélie Couteau-Chardon, et al.. The Proteolytic Inactivation of Protein Z-Dependent Protease Inhibitor by Neutrophil Elastase Might Promote the Procoagulant Activity of Neutrophil Extracellular Traps in Sepsis. Thrombosis and Haemostasis, Schattauer, 2021, Online ahead of print. ⟨10.1055/a-1530-3980⟩. ⟨inserm-03313257⟩

Share

Metrics

Record views

17