Logo Logo
Help
Contact
Switch Language to German
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; Viemann, Dorothee (2014): Alarmins MRP8 and MRP14 Induce Stress Tolerance in Phagocytes under Sterile Inflammatory Conditions. In: Cell Reports, Vol. 9, No. 6: pp. 2112-2123
[img]
Preview
3MB

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.