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Syk phosphorylation – a gravisensitive step in macrophage signalling

Brungs, Sonja and Kolanus, Waldemar and Hemmersbach, Ruth (2015) Syk phosphorylation – a gravisensitive step in macrophage signalling. Cell Communication and Signaling, 13 (9). BioMed Central. DOI: 10.1186/s12964-015-0088-8 ISSN 1478-811X

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Official URL: http://www.biosignaling.com/content/13/1/9


Background: The recognition of pathogen patterns followed by the production of reactive oxygen species (ROS) during the oxidative burst is one of the major functions of macrophages. This process is the first line of defence and is crucial for the prevention of pathogen-associated diseases. There are indications that the immune system of astronauts is impaired during spaceflight, which could result in an increased susceptibility to infections. Several studies have indicated that the oxidative burst of macrophages is highly impaired after spaceflight, but the underlying mechanism remained to be elucidated. Here, we investigated the characteristics of reactive oxygen species production during the oxidative burst after pathogen pattern recognition in simulated microgravity by using a fast-rotating Clinostat to mimic the condition of microgravity. Furthermore, spleen tyrosine kinase (Syk) phosphorylation, which is required for ROS production, and the translocation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) to the nucleus were monitored to elucidate the influence of altered gravity on macrophage signalling. Results: Simulated microgravity leads to significantly diminished ROS production in macrophages upon zymosan, curdlan and lipopolysaccharide stimulation. To address the signalling mechanisms involved, Syk phosphorylation was examined, revealing significantly reduced phosphorylation in simulated microgravity compared to normal gravity (1 g) conditions. In contrast, a later signalling step, the translocation of NF-κB to the nucleus, demonstrated no gravity-dependent alterations. Conclusions: The results obtained in simulated microgravity show that ROS production in macrophages is a highly gravisensitive process, caused by a diminished Syk phosphorylation. In contrast, NF-κB signalling remains consistent in simulated microgravity. This difference reveals that early signalling steps, such as Syk phosphorylation, are affected by microgravity, whereas the lack of effects in later steps might indicate adaptation processes. Taken together, this study clearly demonstrates that macrophages display impaired signalling upon pattern recognition when exposed to simulated microgravity conditions, which if verified in real microgravity this may be one reason why astronauts display higher susceptibility to infections.

Item URL in elib:https://elib.dlr.de/95528/
Document Type:Article
Additional Information:The first author received a Helmholtz Space Life Sciences Research School (SpaceLife) Scholarship. SpaceLife is funded in equal parts by the Helmholtz Association and the German Aerospace Center (DLR).
Title:Syk phosphorylation – a gravisensitive step in macrophage signalling
AuthorsInstitution or Email of AuthorsAuthors ORCID iD
Brungs, SonjaDLR Institute of Aerospace Medicine, Biomedical Research, Cologne, GermanyUNSPECIFIED
Kolanus, WaldemarLaboratory of Molecular Immunology, Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, GermanyUNSPECIFIED
Hemmersbach, RuthDLR Institute of Aerospace Medicine, Biomedical Research, Cologne, GermanyUNSPECIFIED
Date:3 February 2015
Journal or Publication Title:Cell Communication and Signaling
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In ISI Web of Science:Yes
DOI :10.1186/s12964-015-0088-8
Publisher:BioMed Central
Keywords:Host defence, Microgravity, Syk, Clinostat, NF-κB, Macrophage, ROS signaling
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Forschung unter Weltraumbedingungen
DLR - Research theme (Project):R - Vorhaben Biowissenschaftliche Nutzerunterstützung
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Biomedical Research
Deposited By: Duwe, Helmut
Deposited On:10 Mar 2015 11:56
Last Modified:14 Dec 2019 04:28

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