TY  - JOUR
A1  - Janicová, Andrea
A1  - Becker, Nils
A1  - Xu, Baolin
A1  - Wutzler, Sebastian
A1  - Vollrath, Jan Tilmann
A1  - Hildebrand, Frank
A1  - Ehnert, Sabrina
A1  - Marzi, Ingo
A1  - Störmann, Philipp
A1  - Relja, Borna
T1  - Endogenous uteroglobin as intrinsic anti-inflammatory signal modulates monocyte and macrophage subsets distribution upon sepsis induced lung injury
T2  - Frontiers in immunology
N2  - Sepsis is a serious clinical condition which can cause life-threatening organ dysfunction, and has limited therapeutic options. The paradigm of limiting excessive inflammation and promoting anti-inflammatory responses is a simplified concept. Yet, the absence of intrinsic anti-inflammatory signaling at the early stage of an infection can lead to an exaggerated activation of immune cells, including monocytes and macrophages. There is emerging evidence that endogenous molecules control those mechanisms. Here we aimed to identify and describe the dynamic changes in monocyte and macrophage subsets and lung damage in CL57BL/6N mice undergoing blunt chest trauma with subsequent cecal ligation and puncture. We showed that early an increase in systemic and activated Ly6C+CD11b+CD45+Ly6G− monocytes was paralleled by their increased emigration into lungs. The ratio of pro-inflammatory Ly6ChighCD11b+CD45+Ly6G− to patrolling Ly6ClowCD11b+CD45+Ly6G− monocytes significantly increased in blood, lungs and bronchoalveolar lavage fluid (BALF) suggesting an early transition to inflammatory phenotypes during early sepsis development. Similar to monocytes, the level of pro-inflammatory Ly6ChighCD45+F4/80+ macrophages increased in lungs and BALF, while tissue repairing Ly6ClowCD45+F4/80+ macrophages declined in BALF. Levels of inflammatory mediators TNF-α and MCP-1 in blood and RAGE in lungs and BALF were elevated, and besides their boosting of inflammation via the recruitment of cells, they may promote monocyte and macrophage polarization, respectively, toward the pro-inflammatory phenotype. Neutralization of uteroglobin increased pro-inflammatory cytokine levels, activation of inflammatory phenotypes and their recruitment to lungs; concurrent with increased pulmonary damage in septic mice. In in vitro experiments, the influence of uteroglobin on monocyte functions including migratory behavior, TGF-β1 expression, cytotoxicity and viability were proven. These results highlight an important role of endogenous uteroglobin as intrinsic anti-inflammatory signal upon sepsis-induced early lung injury, which modules the early monocyte/macrophages driven inflammation.
KW  - uteroglobin
KW  - CC16
KW  - chest injury
KW  - acute lung injury
KW  - CLP
KW  - sepsis
KW  - monocytes
KW  - macrophages
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51703
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-517032
SN  - 1664-3224
N1  - Copyright © 2019 Janicova, Becker, Xu, Wutzler, Vollrath, Hildebrand, Ehnert, Marzi, Störmann and Relja. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
VL  - 10
IS  - Art. 2276
SP  - 1
EP  - 14
PB  - Frontiers Media
CY  - Lausanne
ER  -