scholarly journals Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Cecilia P. Marin Oyarzún ◽  
Agostina Carestia ◽  
Paola R. Lev ◽  
Ana C. Glembotsky ◽  
Miguel A. Castro Ríos ◽  
...  
2020 ◽  
Vol 4 (2) ◽  
pp. 312-321 ◽  
Author(s):  
Brianna M. Craver ◽  
Gajalakshmi Ramanathan ◽  
Summer Hoang ◽  
Xinyue Chang ◽  
Laura F. Mendez Luque ◽  
...  

Abstract Thrombosis is a major cause of mortality in patients with myeloproliferative neoplasms (MPNs), though there is currently little to offer patients with MPN beyond aspirin and cytoreductive therapies such as hydroxyurea for primary prevention. Thrombogenesis in MPN involves multiple cellular mechanisms, including platelet activation and neutrophil-extracellular trap formation; therefore, an antithrombotic agent that targets one or more of these processes would be of therapeutic benefit in MPN. Here, we treated the JAK2V617F knockin mouse model of polycythemia vera with N-acetylcysteine (NAC), a sulfhydryl-containing compound with broad effects on glutathione replenishment, free radical scavenging, and reducing disulfide bonds, to investigate its antithrombotic effects in the context of MPN. Strikingly, NAC treatment extended the lifespan of JAK2V617F mice without impacting blood counts or splenomegaly. Using an acute pulmonary thrombosis model in vivo, we found that NAC reduced thrombus formation to a similar extent as the irreversible platelet inhibitor aspirin. In vitro analysis of platelet activation revealed that NAC reduced thrombin-induced platelet-leukocyte aggregate formation in JAK2V617F mice. Furthermore, NAC reduced neutrophil extracellular trap formation in primary human neutrophils from patients with MPN as well as healthy controls. These results provide evidence that N-acetylcysteine inhibits thrombosis in JAK2V617F mice and provide a pre-clinical rationale for investigating NAC as a therapeutic to reduce thrombotic risk in MPN.


Shock ◽  
2016 ◽  
Vol 45 (4) ◽  
pp. 393-403 ◽  
Author(s):  
Cláudia V. Araújo ◽  
Clarissa Campbell ◽  
Cassiano F. Gonçalves-de-Albuquerque ◽  
Raphael Molinaro ◽  
Mark J. Cody ◽  
...  

BIO-PROTOCOL ◽  
2017 ◽  
Vol 7 (13) ◽  
Author(s):  
Dongsheng Jiang ◽  
Mona Saffarzadeh ◽  
Karin Scharffetter-Kochanek

2016 ◽  
Vol 184 (3) ◽  
pp. 358-367 ◽  
Author(s):  
J. G. Nel ◽  
A. J. Theron ◽  
C. Durandt ◽  
G. R. Tintinger ◽  
R. Pool ◽  
...  

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