Bioassay for Endothelial Damage Mediators Retrieved by Hemoadsorption
| العنوان: | Bioassay for Endothelial Damage Mediators Retrieved by Hemoadsorption |
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| المؤلفون: | E. Marion Schneider, Sebastian Wiese, Tanja Schulz, Tabea Hein, Hendrik Bracht, Annika Roecker, Ludger Staendker, Jan Münch, Ruediger Gross, Maximilian Denzinger, Manfred Weiss, Michael K. Georgieff, Julian M. Schneider, Keno Ehlers, Eberhard Barth |
| المصدر: | Scientific Reports, Vol 9, Iss 1, Pp 1-13 (2019) Scientific Reports |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Programmed cell death, Vinyl Compounds, Cell Survival, lcsh:Medicine, Apoptosis, Inflammation, Ligands, Article, Proinflammatory cytokine, 03 medical and health sciences, Adenosine Triphosphate, 0302 clinical medicine, Sepsis, medicine, Alarmins, Humans, Bioassay, lcsh:Science, Aged, Multidisciplinary, Blood proteins, Chemistry, Microcirculation, Pathogen-associated molecular pattern, lcsh:R, Endothelial Cells, 030208 emergency & critical care medicine, Shock, Septic, Cell biology, Oxygen, Endothelial stem cell, 030104 developmental biology, Preclinical research, Nucleic acid, Cytokines, Polystyrenes, Biological Assay, Female, lcsh:Q, Adsorption, Endothelium, Vascular, medicine.symptom |
| الوصف: | Hemoadsorption devices are used to treat septic shock by adsorbing inflammatory cytokines and as yet incompletely defined danger and pathogen associated molecular patterns. In an ideal case, hemoadsorption results in immediate recovery of microvascular endothelial cells’ (mEC) function and rapid recovery from catecholamine-dependency and septic shock. We here tested a single device, which consists of polystyrene-divinylbenzene core particles of 450 μm diameter with a high affinity for hydrophobic compounds. The current study aimed at the proof of concept that endothelial-specific damage mediators are adsorbed and can be recovered from hemoadsorption devices. Because of excellent clinical experience, we tested protein fractions released from a hemoadsorber in a novel endothelial bioassay. Video-based, long-term imaging of mEC proliferation and cell death were evaluated and combined with apoptosis and ATP measurements. Out of a total of 39 fractions recovered from column fractionation, we identified 3 fractions that caused i) inhibition of mEC proliferation, ii) increased cell death and iii) induction of apoptosis in mEC. When adding these 3 fractions to mEC, their ATP contents were reduced. These fractions contained proteins of approximately 15 kDa, and high amounts of nucleic acid, which was at least in part oxidized. The efficacy for endothelial cell damage prevention by hemoadsorption can be addressed by a novel endothelial bioassay and long-term video observation procedures. Protein fractionation of the hemoadsorption devices used is feasible to study and define endothelial damage ligands on a molecular level. The results suggest a significant effect by circulating nucleic acids – bound to an as yet undefined protein, which may constitute a major danger-associated molecular pattern (DAMP) in the exacerbation of inflammation when patients experience septic shock. Hemoadsorption devices may thus limit endothelial damage, through the binding of nucleic acid-bearing aggregates and thus contribute to improved endothelial barrier function. |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::631e7fac035d0c658a0de8e232228901Test https://doi.org/10.1038/s41598-019-50517-1Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....631e7fac035d0c658a0de8e232228901 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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