Artikel
Protection from septic shock in mice with genetic inactivation of procalcitonin
Suche in Medline nach
Autoren
-
Johannes Keller
- Charité Universitätsmedizin Berlin, Centrum für Muskuloskeletale Chirurgie, Berlin, Germany
-
Anke Jeschke
- Universitätsklinikum Hamburg-Eppendorf, Institut für Osteologie und Biomechanik, Hamburg, Germany
-
Christian Kleber
- University Center of Orthopaedics and Traumatology, University Medicine Carl Gustav Carus Dresden, TU Dresden, Dresden, Germany
-
Serafeim Tsitsilonis
- Charité Universitätsmedizin Berlin, Centrum für Muskuloskeletale Chirurgie, Berlin, Germany
-
Philipp Schwabe
- Charité Universitätsmedizin Berlin, Centrum für Muskuloskeletale Chirurgie, Berlin, Germany
-
Klaus-Dieter Schaser
- University Center of Orthopaedics and Traumatology, University Medicine Carl Gustav Carus Dresden, TU Dresden, Dresden, Germany
-
Michael Amling
- Universitätsklinikum Hamburg-Eppendorf, Institut für Osteologie und Biomechanik, Hamburg, Germany
-
Thorsten Schinke
- Universitätsklinikum Hamburg-Eppendorf, Institut für Osteologie und Biomechanik, Hamburg, Germany
| Veröffentlicht: | 10. Oktober 2016 |
|---|
Gliederung
Text
Objectives: Sepsis is a common complication following polytrauma with a high mortality rate. Procalcitonin (PCT) represents the most sensitive and specific marker of sepsis, however its pathophysiological function remains unclear.
Methods: To study a potential mediator role of PCT in experimental sepsis, mice deficient in Calca, encoding the related proteins PCT, calcitonin (CT) and calcitonin gene-related peptide alpha (αCgrp) were challenged with intraperitoneal lipopolysaccharide to induce septic shock. To rule out an influence of CT and αCgrp signaling, mice lacking the calcitonin receptor (CTR) or αCgrp were used as controls. Blood samples were analyzed by ELISA whereas local events were monitored using qRT-PCR, immunohistochemistry and FACS analyses. For cell culture experiments, primary macrophages were generated from bone marrow cells using M-CSF.
Results and Conclusion: Systemic endotoxemia resulted in a ubiquitous and significant induction of Calca expression. Blood analyses revealed increased levels of circulating PCT and αCgrp during septic shock, while CT levels remained normal. Mice deficient in Calca, representing PCT-deficiency, displayed increased survival during lethal endotoxemia compared to WT littermates. In contrast, mice exclusively lacking CTR or αCgrp showed no overt phenotype. In vivo, the expression of the putative PCT receptor, calcitonin receptor-like receptor, was found predominantly in the lung, coinciding with reduced pulmonary macrophage influx in septic Calca-deficient mice. In vitro, PCT positively regulated the expression of pro-inflammatory cytokines including Interleukin-1 and Interleukin-6 in macrophages. This study provides evidence for a mediator role of PCT in septic shock with therapeutic potential for affected patients.
