Granulocyte colony-stimulating factor (G-CSF) increases histone-complexed DNA plasma levels in healthy volunteers



Schoergenhofer, Christian, Schwameis, Michael, Wohlfarth, Philipp, Brostjan, Christine, Abrams, Simon T, Toh, Cheng-Hock and Jilma, Bernd
(2017) Granulocyte colony-stimulating factor (G-CSF) increases histone-complexed DNA plasma levels in healthy volunteers. CLINICAL AND EXPERIMENTAL MEDICINE, 17 (2). pp. 243-249.

[img] Text
gcsf hcDNA paper accepted.docx - Author Accepted Manuscript

Download (92kB)

Abstract

Granulocyte colony-stimulating factor (G-CSF) is an activator of neutrophil granulocytes. Neutrophil extracellular traps are a defensive mechanism consisting of neutrophils, platelets, DNA, histones and antimicrobial proteins. This study was performed to determine whether G-CSF increases histone-complexed DNA in the plasma of healthy volunteers. In total, 51 healthy volunteers (25 males and 26 females) were treated with G-CSF (18 with 300 µg single dose i.v., 27 with 5 µg/kg s.c. for 4 days) and six participants received a placebo. Histone-complexed DNA was measured by enzyme immunoassay in plasma samples at predefined time points (0, 2, 4, 6, 24 h after single dose, day 1, day 2 and day 5 after repeated doses). Histone levels were quantified by Western blotting. A single dose of G-CSF rapidly increased hc-DNA by about 50 % (p < 0.05 for 2-24 h). After repeated doses the increase was even more pronounced: hc-DNA increased by about 50 % (3.0 ± 0.9, p < 0.001 after 24 h and about fourfold after 96 h (p < 0.001)). A statistical significant increase in histone levels was detected as early as 4 h after G-CSF injection (0.43 ± 0.2 vs. 1.08 ± 0.3 µg/ml; p = 0.034). In the placebo group no significant changes occurred. Moreover, significantly higher levels of hc-DNA were measured in male compared to female subjects (226 ± 43 vs. 84 ± 19, p < 0.001). G-CSF injection substantially increases hc-DNA levels in healthy volunteers. There is a significant gender difference in hc-DNA at the baseline.

Item Type: Article
Uncontrolled Keywords: G-CSF, Histones, NETs, Gender, Neutrophils
Depositing User: Symplectic Admin
Date Deposited: 18 Jul 2016 15:19
Last Modified: 19 Jan 2023 07:33
DOI: 10.1007/s10238-016-0413-6
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3002410