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2017 ; 7
(1
): 8972
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CitH3: a reliable blood biomarker for diagnosis and treatment of endotoxic shock
#MMPMID28827548
Pan B
; Alam HB
; Chong W
; Mobley J
; Liu B
; Deng Q
; Liang Y
; Wang Y
; Chen E
; Wang T
; Tewari M
; Li Y
Sci Rep
2017[Aug]; 7
(1
): 8972
PMID28827548
show ga
Current biomarkers for sepsis are limited by their non-specificity, short
half-life, and insensitive response to therapy. Recently, we have demonstrated
that citrullinated histone H3(CitH3) is released into the blood from neutrophil
extracellular traps(NETs) in response to severe infection, and CitH3 may be a
potential biomarker for sepsis. In the present study, we found that NET
components were released in mouse models of both lipopolysaccharide(LPS)-induced
shock (LPSS) and hemorrhagic shock (HS). To further quantify CitH3 in the NETs,
we established a CitH3 specific enzyme-linked immunosorbent assay. Circulating
CitH3 was found to be elevated only in LPSS but not in HS. Importantly, blood
CitH3 was detected 30?minutes after LPS insult, and remained elevated for
24?hours (period of the highest mortality). Treatment of endotoxic mice with
YW3-56, a peptidylarginine deiminase-2/4 inhibitor, significantly diminished
levels of CitH3 in the blood. Interleukin-1? did not respond to LPS early, and
interleukin-1? and interleukin-6 fluctuated although they responded to treatment.
Procalcitonin reacted to LPS insult late. Compared to CitH3, these biomarkers
were non-specifically induced in LPSS and HS. Collectively, our results
demonstrate that YW3-56 protects animals from LPSS, and CitH3 is a reliable
biomarker due to its early appearance, specificity, duration, and response to
therapeutic intervention.