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Article

Heparin-Functionalized Adsorbents Eliminate Central Effectors of Immunothrombosis, including Platelet Factor 4, High-Mobility Group Box 1 Protein and Histones

1
Center for Biomedical Technology, Department for Biomedical Research, Danube University Krems, 3500 Krems, Austria
2
Clinic for Blood Group Serology and Transfusion Medicine, Medical University of Vienna, 1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
Academic Editors: Kerstin Jurk, Marijke J. E. Kuijpers and Johan W. M. Heemskerk
Int. J. Mol. Sci. 2022, 23(3), 1823; https://doi.org/10.3390/ijms23031823
Received: 21 December 2021 / Revised: 31 January 2022 / Accepted: 1 February 2022 / Published: 5 February 2022
Inflammation and thrombosis are closely intertwined in numerous disorders, including ischemic events and sepsis, as well as coronavirus disease 2019 (COVID-19). Thrombotic complications are markers of disease severity in both sepsis and COVID-19 and are associated with multiorgan failure and increased mortality. Immunothrombosis is driven by the complement/tissue factor/neutrophil axis, as well as by activated platelets, which can trigger the release of neutrophil extracellular traps (NETs) and release further effectors of immunothrombosis, including platelet factor 4 (PF4/CXCL4) and high-mobility box 1 protein (HMGB1). Many of the central effectors of deregulated immunothrombosis, including activated platelets and platelet-derived extracellular vesicles (pEVs) expressing PF4, soluble PF4, HMGB1, histones, as well as histone-decorated NETs, are positively charged and thus bind to heparin. Here, we provide evidence that adsorbents functionalized with endpoint-attached heparin efficiently deplete activated platelets, pEVs, PF4, HMGB1 and histones/nucleosomes. We propose that this elimination of central effectors of immunothrombosis, rather than direct binding of pathogens, could be of clinical relevance for mitigating thrombotic complications in sepsis or COVID-19 using heparin-functionalized adsorbents. View Full-Text
Keywords: adsorption; COVID-19; extracellular vesicles; heparin; immunothrombosis; neutrophil extracellular traps; platelet factor 4; platelets; sepsis adsorption; COVID-19; extracellular vesicles; heparin; immunothrombosis; neutrophil extracellular traps; platelet factor 4; platelets; sepsis
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MDPI and ACS Style

Ebeyer-Masotta, M.; Eichhorn, T.; Weiss, R.; Semak, V.; Lauková, L.; Fischer, M.B.; Weber, V. Heparin-Functionalized Adsorbents Eliminate Central Effectors of Immunothrombosis, including Platelet Factor 4, High-Mobility Group Box 1 Protein and Histones. Int. J. Mol. Sci. 2022, 23, 1823. https://doi.org/10.3390/ijms23031823

AMA Style

Ebeyer-Masotta M, Eichhorn T, Weiss R, Semak V, Lauková L, Fischer MB, Weber V. Heparin-Functionalized Adsorbents Eliminate Central Effectors of Immunothrombosis, including Platelet Factor 4, High-Mobility Group Box 1 Protein and Histones. International Journal of Molecular Sciences. 2022; 23(3):1823. https://doi.org/10.3390/ijms23031823

Chicago/Turabian Style

Ebeyer-Masotta, Marie, Tanja Eichhorn, René Weiss, Vladislav Semak, Lucia Lauková, Michael B. Fischer, and Viktoria Weber. 2022. "Heparin-Functionalized Adsorbents Eliminate Central Effectors of Immunothrombosis, including Platelet Factor 4, High-Mobility Group Box 1 Protein and Histones" International Journal of Molecular Sciences 23, no. 3: 1823. https://doi.org/10.3390/ijms23031823

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