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

作者：Austermann Judith^*; Friesenhagen Judith; Fassl Selina Kathleen; Ortkras Theresa; Burgmann Johanna; Barczyk Kahlert Katarzyna; Faist Eugen; Zedler Siegfried; Pirr Sabine; Rohde Christian; Mueller Tidow Carsten; von Koeckritz Blickwede Maren; von Kaisenberg Constantin S; Flohe Stefanie B; Ulas Thomas; Schultze Joachim L; Roth Johannes; Vogl Thomas; Viemann Dorothee

来源：Cell Reports, 2014, 9(6): 2112-2123.

DOI：10.1016/j.celrep.2014.11.020

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.

• 出版日期2014-12-24