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Netosis and Inflammasomes in Large Vessel Occlusion Thrombi

Authors :
Stephanie H. Chen
Xavier O. Scott
Yoandy Ferrer Marcelo
Vania W. Almeida
Patricia L. Blackwelder
Dileep R. Yavagal
Eric C. Peterson
Robert M. Starke
W. Dalton Dietrich
Robert W. Keane
Juan Pablo de Rivero Vaccari
Source :
Frontiers in Pharmacology, Frontiers in Pharmacology, Vol 11 (2021)
Publication Year :
2021
Publisher :
Frontiers Media SA, 2021.

Abstract

The inflammatory response appears to play a critical role in clotting in which neutrophil extracellular traps (NETs) are the major drivers of thrombosis in acute ischemic stroke (AIS). The inflammasome is an innate immune complex involved in the activation of interleukin (IL)-18 and IL-1β through caspase-1, but whether the inflammasome plays a role in NETosis in AIS remains poorly understood. Here we assessed the levels of inflammasome signaling proteins in NETs and their association with clinical and procedural outcomes of mechanical thrombectomy for AIS. Electron microscopy and immunofluorescence indicate the presence of NETs in thrombi of patients with AIS. Moreover, the inflammasome signaling proteins caspase-1 and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) were also present in clots associated with the marker of NETosis citrullinated histone 3H (CitH3). Analysis of protein levels by a simple plex assay show that caspase-1, ASC and interleukin (IL)-1β were significantly elevated in clots when compared to plasma of AIS patients and healthy controls, while IL-18 levels were lower. Moreover, multivariate analyses show that IL-1β levels in clots contribute to the number of passes to achieve complete recanalization, and that ASC, caspase-1 and IL-18 are significant contributors to time to recanalization. Thus, inflammasome proteins are elevated in NETs present in thrombi of patients with AIS that contribute to poor outcomes following stroke.

Details

Language :
English
ISSN :
16639812
Volume :
11
Database :
OpenAIRE
Journal :
Frontiers in Pharmacology
Accession number :
edsair.doi.dedup.....61fa0a272cbc9af00aa2e45ddba446ad
Full Text :
https://doi.org/10.3389/fphar.2020.607287