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10.3390/ijms23031823

http://scihub22266oqcxt.onion/10.3390/ijms23031823
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suck abstract from ncbi


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pmid35163743      Int+J+Mol+Sci 2022 ; 23 (3): ä
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  • Heparin-Functionalized Adsorbents Eliminate Central Effectors of Immunothrombosis, including Platelet Factor 4, High-Mobility Group Box 1 Protein and Histones #MMPMID35163743
  • Ebeyer-Masotta M; Eichhorn T; Weiss R; Semak V; Laukova L; Fischer MB; Weber V
  • Int J Mol Sci 2022[Feb]; 23 (3): ä PMID35163743show ga
  • 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.
  • |Blood Coagulation/physiology[MESH]
  • |Blood Platelets/metabolism[MESH]
  • |Blood Proteins/*isolation & purification/metabolism[MESH]
  • |COVID-19/metabolism[MESH]
  • |Extracellular Traps/immunology/metabolism[MESH]
  • |HMGB Proteins/isolation & purification/metabolism[MESH]
  • |HMGB1 Protein/isolation & purification/metabolism[MESH]
  • |Heparin/metabolism/*pharmacology[MESH]
  • |Histones/isolation & purification/metabolism[MESH]
  • |Humans[MESH]
  • |Neutrophils/metabolism[MESH]
  • |Platelet Activation/immunology[MESH]
  • |Platelet Factor 4/isolation & purification/metabolism[MESH]
  • |SARS-CoV-2/pathogenicity[MESH]
  • |Sepsis/blood/metabolism[MESH]
  • |Thromboinflammation/*drug therapy[MESH]
  • |Thromboplastin/metabolism[MESH]


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