CitH3: a reliable blood biomarker for diagnosis and treatment of endotoxic shock
| Autor: | Hasan B. Alam, Wei Chong, Baihong Pan, Baoling Liu, Tianbing Wang, Qiufang Deng, Muneesh Tewari, Eric Chen, Yongqing Li, James Mobley, Yinjian Liang, Yanming Wang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Time Factors Lipopolysaccharide Science Enzyme-Linked Immunosorbent Assay Arginine Extracellular Traps Sensitivity and Specificity Procalcitonin Article Sepsis Histones 03 medical and health sciences Histone H3 chemistry.chemical_compound Mice 0302 clinical medicine 2-Naphthylamine Medicine Animals Immunologic Factors Multidisciplinary business.industry Diagnostic Tests Routine Citrullination Neutrophil extracellular traps medicine.disease Shock Septic Disease Models Animal 030104 developmental biology Treatment Outcome chemistry 030220 oncology & carcinogenesis Shock (circulatory) Immunology Biomarker (medicine) lipids (amino acids peptides and proteins) medicine.symptom business Protein Processing Post-Translational Biomarkers |
| Zdroj: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-8 (2017) |
| ISSN: | 2045-2322 |
| Popis: | 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-1β did not respond to LPS early, and interleukin-1β 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. |
| Databáze: | OpenAIRE |
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