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

被引：106

作者：

Austermann, Judith ^{[1
,2
]}

Friesenhagen, Judith ^{[3
]}

Fassl, Selina Kathleen ^{[1
]}

Ortkras, Theresa ^{[1
]}

Burgmann, Johanna ^{[3
]}

Barczyk-Kahlert, Katarzyna ^{[1
]}

Faist, Eugen ^{[4
,5
]}

Zedler, Siegfried ^{[4
,5
]}

Pirr, Sabine ^{[3
]}

Rohde, Christian ^{[6
]}

Mueller-Tidow, Carsten ^{[6
]}

von Koeckritz-Blickwede, Maren ^{[7
]}

von Kaisenberg, Constantin S. ^{[8
]}

Flohe, Stefanie B. ^{[9
]}

Ulas, Thomas ^{[10
]}

Schultze, Joachim L. ^{[10
]}

Roth, Johannes ^{[1
,2
]}

Vogl, Thomas ^{[2
]}

Viemann, Dorothee ^{[3
]}

机构：

[1] Univ Munster, Inst Immunol, D-48149 Munster, Germany

[2] Univ Munster, Interdisciplinary Ctr Clin Res, D-48149 Munster, Germany

[3] Hannover Med Sch, Dept Pediat Pneumol Allergy & Neonatol, D-30625 Hannover, Germany

[4] Univ Munich, Dept Surg, D-81377 Munich, Germany

[5] Univ Munich, Clin Study Ctr, D-81377 Munich, Germany

[6] Univ Med Ctr Halle Saale, Internal Med Clin 4, Dept Mol Haematol & Oncol, D-06120 Halle, Germany

[7] Univ Vet Med Hannover, Dept Physiol Chem, D-30625 Hannover, Germany

[8] Hannover Med Sch, Dept Gynaecol & Prenatal Med, D-30625 Hannover, Germany

[9] Univ Duisburg Essen, Univ Hosp Essen, Dept Trauma Surg, D-45147 Essen, Germany

[10] Univ Bonn, LIMES Inst, D-53115 Bonn, Germany

来源：

CELL REPORTS | 2014年 / 9卷 / 06期

关键词：

JUVENILE RHEUMATOID-ARTHRITIS; EARLY-ONSET SEPSIS; ENDOTOXIN TOLERANCE; MYELOID DIFFERENTIATION; INJURY SEVERITY; PROTEINS; 8; S100A9; MECHANISMS; EXPRESSION; PATHWAY;

D O I：

10.1016/j.celrep.2014.11.020

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页码：2112 / 2123

页数：12

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