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Alarmins MRP8 and MRP14 induce stress tolerance in phagocytes under sterile inflammatory conditions.
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; von Köckritz-Blickwede, Maren; von Kaisenberg, Constantin S; Flohé, Stefanie B; Ulas, Thomas; Schultze, Joachim L; Roth, Johannes; Vogl, Thomas; Viemann, Dorothee.
Affiliation
  • Austermann J; Institute of Immunology, University of Münster, 48149 Münster, Germany; Interdisciplinary Centre for Clinical Research, University of Münster, 48149 Münster, Germany. Electronic address: judithaustermann@gmx.de.
  • Friesenhagen J; Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, 30625 Hannover, Germany.
  • Fassl SK; Institute of Immunology, University of Münster, 48149 Münster, Germany.
  • Ortkras T; Institute of Immunology, University of Münster, 48149 Münster, Germany.
  • Burgmann J; Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, 30625 Hannover, Germany.
  • Barczyk-Kahlert K; Institute of Immunology, University of Münster, 48149 Münster, Germany.
  • Faist E; Department of Surgery and Clinical Study Center, Ludwig-Maximilian University, 81377 Munich, Germany.
  • Zedler S; Department of Surgery and Clinical Study Center, Ludwig-Maximilian University, 81377 Munich, Germany.
  • Pirr S; Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, 30625 Hannover, Germany.
  • Rohde C; Department of Molecular Haematology and Oncology, Internal Medicine Clinic IV, University Medical Center Halle (Saale), 06120 Halle, Germany.
  • Müller-Tidow C; Department of Molecular Haematology and Oncology, Internal Medicine Clinic IV, University Medical Center Halle (Saale), 06120 Halle, Germany.
  • von Köckritz-Blickwede M; Department of Physiological Chemistry, University of Veterinary Medicine Hannover, 30625 Hannover, Germany.
  • von Kaisenberg CS; Department of Gynaecology and Prenatal Medicine, Medical School Hannover, 30625 Hannover, Germany.
  • Flohé SB; Surgical Research, Department of Trauma Surgery, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
  • Ulas T; Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
  • Schultze JL; Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
  • Roth J; Institute of Immunology, University of Münster, 48149 Münster, Germany; Interdisciplinary Centre for Clinical Research, University of Münster, 48149 Münster, Germany.
  • Vogl T; Institute of Immunology, University of Münster, 48149 Münster, Germany; Interdisciplinary Centre for Clinical Research, University of Münster, 48149 Münster, Germany.
  • Viemann D; Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, 30625 Hannover, Germany.
Cell Rep ; 9(6): 2112-23, 2014 Dec 24.
Article in En | MEDLINE | ID: mdl-25497086
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Phagocytes / Calgranulin A / Calgranulin B / Immune Tolerance Type of study: Prognostic_studies Limits: Adult / Aged / Animals / Female / Humans / Male / Middle aged Language: En Journal: Cell Rep Year: 2014 Document type: Article Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Phagocytes / Calgranulin A / Calgranulin B / Immune Tolerance Type of study: Prognostic_studies Limits: Adult / Aged / Animals / Female / Humans / Male / Middle aged Language: En Journal: Cell Rep Year: 2014 Document type: Article Country of publication: United States