Circulating histones contribute to monocyte and MDW alterations as common mediators in classical and COVID-19 sepsis.

Autor: Ligi D; Unit of Clinical Biochemistry, Section of Biochemistry and Biotechnology, Department of Biomolecular Sciences -DISB, University of Urbino Carlo Bo, Via A. Saffi, 2, 61029, Urbino, Italy., Lo Sasso B; Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, BiND, University of Palermo, Via del Vespro, 90127, Palermo, Italy., Giglio RV; Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, BiND, University of Palermo, Via del Vespro, 90127, Palermo, Italy., Maniscalco R; Unit of Clinical Biochemistry, Section of Biochemistry and Biotechnology, Department of Biomolecular Sciences -DISB, University of Urbino Carlo Bo, Via A. Saffi, 2, 61029, Urbino, Italy., DellaFranca C; Unit of Clinical Biochemistry, Section of Biochemistry and Biotechnology, Department of Biomolecular Sciences -DISB, University of Urbino Carlo Bo, Via A. Saffi, 2, 61029, Urbino, Italy., Agnello L; Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, BiND, University of Palermo, Via del Vespro, 90127, Palermo, Italy., Ciaccio M; Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, BiND, University of Palermo, Via del Vespro, 90127, Palermo, Italy.; Department and U.O.C. Laboratory Medicine, University Hospital 'Paolo Giaccone' of Palermo, Palermo, Italy., Mannello F; Unit of Clinical Biochemistry, Section of Biochemistry and Biotechnology, Department of Biomolecular Sciences -DISB, University of Urbino Carlo Bo, Via A. Saffi, 2, 61029, Urbino, Italy. ferdinando.mannello@uniurb.it.
Jazyk: angličtina
Zdroj: Critical care (London, England) [Crit Care] 2022 Aug 30; Vol. 26 (1), pp. 260. Date of Electronic Publication: 2022 Aug 30.
DOI: 10.1186/s13054-022-04138-2
Abstrakt: Objective: Histone proteins are physiologically involved in DNA packaging and gene regulation but are extracellularly released by neutrophil/monocyte extracellular traps and mediate thrombo-inflammatory pathways, associated to the severity of many human pathologies, including bacterial/fungal sepsis and COVID-19. Prominent and promising laboratory features in classic and viral sepsis emphasize monocyte distribution width (MDW), due to its ability to distinguish and stratify patients at higher risk of critical conditions or death. No data are available on the roles of histones as MDW modifiers.
Design: Comparison of MDW index was undertaken by routine hematology analyzer on whole blood samples from patients with COVID-19 and Sepsis. The impact of histones on the MDW characteristics was assessed by the in vitro time-dependent treatment of healthy control whole blood with histones and histones plus lipopolysaccharide to simulate viral and classical sepsis, respectively.
Measurements and Main Results: We demonstrated the breadth of early, persistent, and significant increase of MDW index in whole blood from healthy subject treated in vitro with histones, highlighting changes similar to those found in vivo in classic and viral sepsis patients. These findings are mechanistically associated with the histone-induced modifications of cell volume, cytoplasmic granularity and vacuolization, and nuclear structure alterations of the circulating monocyte population.
Conclusions: Histones may contribute to the pronounced and persistent monocyte alterations observed in both acute classical and viral sepsis. Assessment of the biological impact of circulating histone released during COVID-19 and sepsis on these blood cells should be considered as key factor modulating both thrombosis and inflammatory processes, as well as the importance of neutralization of their cytotoxic and procoagulant activities by several commercially available drugs (e.g., heparins and heparinoids).
(© 2022. The Author(s).)
Databáze: MEDLINE
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