Alarmins MRP8 and MRP14 Induce Stress Tolerance in Phagocytes under Sterile Inflammatory Conditions
| Autor: | Austermann, Judith, Friesenhagen, Judith, Fassl, Selina Kathleen, Petersen, Beatrix, Ortkras, Theresa, Burgmann, Johanna, Barczyk-Kahlert, Katarzyna, Faist, Eugen, Zedler, Siegfried, Pirr, Sabine, Rohde, Christian, Müller-Tidow, Carsten, vonKöckritz-Blickwede, Maren, vonKaisenberg, Constantin S., Flohe, Stefanie, Ulas, Thomas, Schultze, Joachim L., Roth, Johannes, Vogl, Thomas, Viemann, Dorothee, von Köckritz-Blickwede, Maren, von Kaisenberg, Constantin S., Flohé, Stefanie B. |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Phagocyte Medizin Stimulation Endogeny General Biochemistry Genetics and Molecular Biology Cell Line Sepsis Mice Stress Physiological Immune Tolerance medicine Animals Calgranulin B Humans Calgranulin A Receptor lcsh:QH301-705.5 Cells Cultured Aged Inflammation Phagocytes business.industry Septic shock NF-kappa B Middle Aged Chromatin Assembly and Disassembly medicine.disease Shock Septic Chromatin medicine.anatomical_structure lcsh:Biology (General) Immunology TLR4 Female Burns business |
| Zdroj: | Cell Reports, Vol 11, Iss 5, p 849 (2015) Cell Reports, Vol 9, Iss 6, Pp 2112-2123 (2014) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2015.04.040 |
| Popis: | Hyporesponsiveness by phagocytes is a well-known phenomenon in sepsis that is frequently induced by low-dose endotoxin stimulation of Toll-like receptor 4 (TLR4) but can also be found under sterile inflammatory conditions. We now demonstrate that the endogenous alarmins MRP8 and MRP14 induce phagocyte hyporesponsiveness via chromatin modifications in a TLR4-dependent manner that results in enhanced survival to septic shock in mice. During sterile inflammation, polytrauma and burn trauma patients initially present with high serum concentrations of myeloid-related proteins (MRPs). Human neonatal phagocytes are primed for hyporesponsiveness by increased peripartal MRP concentrations, which was confirmed in murine neonatal endotoxinemia in wild-type and MRP14(-/-) mice. Our data therefore indicate that alarmin-triggered phagocyte tolerance represents a regulatory mechanism for the susceptibility of neonates during systemic infections and sterile inflammation. OA gold |
| Databáze: | OpenAIRE |
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