Circulating H3Cit is elevated in a human model of endotoxemia and can be detected bound to microvesicles

Scientific Reports
Sofie Paues GöransonFariborz Mobarrez

Abstract

Early diagnosis of sepsis is crucial since prompt interventions decrease mortality. Citrullinated histone H3 (H3Cit), released from neutrophil extracellular traps (NETs) upon binding of platelets to neutrophils following endotoxin stimulation, has recently been proposed a promising blood biomarker in sepsis. Moreover, microvesicles (MVs), which are released during cell activation and apoptosis and carry a variety of proteins from their parental cells, have also been shown to be elevated in sepsis. In a randomized and placebo-controlled human model of endotoxemia (lipopolysaccharide injection; LPS), we now report significant LPS-induced elevations of circulating H3Cit in 22 healthy individuals. We detected elevations of circulating H3Cit by enzyme-linked immunosorbent assay (ELISA), as well as bound to MVs quantified by flow cytometry. H3Cit-bearing MVs expressed neutrophil and/or platelet surface markers, indicating platelet-neutrophil interactions. In addition, in vitro experiments revealed that H3Cit can bind to phosphatidylserine exposed on platelet derived MVs. Taken together; our results demonstrate that NETs can be detected in peripheral blood during endotoxemia by two distinct H3Cit-specific methods. Furthermore, we prop...Continue Reading

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Citations

Jul 19, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Charlotte ThålinHåkan Wallén
May 13, 2020·Epigenomics·Jesús Beltrán-GarcíaJosé Luis García-Giménez
Sep 11, 2019·Scandinavian Journal of Clinical and Laboratory Investigation·Sam KafianFariborz Mobarrez
Jan 28, 2020·Platelets·Ricardo M GómezMirta Schattner
Jul 13, 2020·Journal of Thrombosis and Haemostasis : JTH·Charlotte ThålinAndrea L Johnstone
Mar 12, 2021·Thrombosis and Haemostasis·Xiaofeng CaiAlireza R Rezaie
Jun 8, 2021·Biochemical and Biophysical Research Communications·Peng AiGe Jin
Dec 30, 2021·Vestnik otorinolaringologii·V M SvistushkinK V Eremeeva

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Methods Mentioned

BETA
ELISA
flow cytometry
flow

Software Mentioned

SPSS

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis