Alarmins MRP8 and MRP14 Induce Stress Tolerance in Phagocytes under Sterile Inflammatory Conditions

Austermann, Judith; Friesenhagen, Judith; Fassl, Selina Kathleen; Ortkras, Theresa; Burgmann, Johanna; Barczyk-Kahlert, Katarzyna; Faist, Eugen; Zedler, Siegfried; Pirr, Sabine; Rohde, Christian; Müller-Tidow, Carsten; Koeckritz-Blickwede, Maren von; Kaisenberg, Constantin S. von; Flohe, Stefanie B.; Ulas, Thomas; Schultze, Joachim L.; Roth, Johannes; Vogl, Thomas und Viemann, Dorothee (2014): Alarmins MRP8 and MRP14 Induce Stress Tolerance in Phagocytes under Sterile Inflammatory Conditions. In: Cell Reports, Bd. 9, Nr. 6: S. 2112-2123

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2211-1247
• Sprache: Englisch