Organ Distribution of Histones after Intravenous Infusion of FITC-Histones or after Sepsis
Autor: | Firas S. Zetoune, Anuska V. Andjelkovic, Lawrence Jajou, Peter A. Ward, Fatemeh Fattahi, Jamison J. Grailer |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Male
Neutrophils Immunology Cell Biology Extracellular Traps Article Sepsis Histones chemistry.chemical_compound Mice medicine Animals Humans Infusions Intravenous Cecum Lung Cells Cultured Innate immune system Microscopy Confocal Neutrophil extracellular traps medicine.disease Molecular biology In vitro Mice Inbred C57BL Cytosol Disease Models Animal Histone medicine.anatomical_structure chemistry Liver biology.protein Macrophages Peritoneal DNA Fluorescein-5-isothiocyanate |
Popis: | Histones appear in plasma during infectious or non-infectious sepsis and are associated with multiorgan injury. In the current studies, intravenous infusion of histones resulted in their localization in major organs. In vitro exposure of mouse macrophages to histones caused a buildup of histones on cell membranes followed by localization into cytosol and into the nucleus. After polymicrobial sepsis (cecal ligation and puncture, CLP), histones appeared in plasma as well as in a multiorgan pattern, peaking at 8 hr followed by decline. In lungs, histones and neutrophils appeared together, with evidence for formation of neutrophil extracellular traps (NETs), which represent an innate immune response to trap and kill bacteria and other infectious agents. In liver, there was intense NET formation, featuring linear patterns containing histones and strands of DNA. When neutrophils were activated in vitro with C5a or phorbol myristate acetate, NET formation ensued. While formation of NETs represents entrapment and killing of infectious agents, the simultaneous release from neutrophils of histones often results in tissue/organ damage. |
Databáze: | OpenAIRE |
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