The Proteolytic Inactivation of Protein Z-Dependent Protease Inhibitor by Neutrophil Elastase Might Promote the Procoagulant Activity of Neutrophil Extracellular Traps in Sepsis - Archive ouverte HAL Access content directly
Journal Articles Thrombosis and Haemostasis Year : 2021

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

(1) , (1) , (2, 3, 4) , (5, 6) , (7) , (8, 6) , (8, 6, 9) , (1) , (10) , (8, 6, 9) , (1) , (7, 11) , (1, 10) , (2, 3, 12) , (1, 13)
1
2
3
4
5
6
7
8
9
10
11
12
13
Elsa P Bianchini
  • Function : Author
  • PersonId : 1106900
Cécile V Denis

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.
Fichier principal
Vignette du fichier
second revision-déposée dans HAL.pdf (630.59 Ko) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

inserm-03313257 , version 1 (03-08-2021)

Identifiers

Cite

Elsa P 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, 2021, Online ahead of print. ⟨10.1055/a-1530-3980⟩. ⟨inserm-03313257⟩
101 View
105 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More