Schön, Michael P.

[["dc.bibliographiccitation.artnumber","12"],["dc.bibliographiccitation.journal","Frontiers in Immunology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.affiliation","Neubert, Elsa; 1Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Senger-Sander, Susanne N.; 1Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Manzke, Veit S.; 1Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Busse, Julia; 1Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Polo, Elena; 2Institute of Physical Chemistry, University of Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Scheidmann, Sophie E. F.; 1Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Schön, Michael P.; 1Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Kruss, Sebastian; 2Institute of Physical Chemistry, University of Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Erpenbeck, Luise; 1Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.author","Neubert, Elsa"],["dc.contributor.author","Senger-Sander, Susanne N."],["dc.contributor.author","Manzke, Veit S."],["dc.contributor.author","Busse, Julia"],["dc.contributor.author","Polo, Elena"],["dc.contributor.author","Scheidmann, Sophie E. F."],["dc.contributor.author","Schön, Michael P."],["dc.contributor.author","Kruss, Sebastian"],["dc.contributor.author","Erpenbeck, Luise"],["dc.date.accessioned","2019-07-09T11:50:03Z"],["dc.date.available","2019-07-09T11:50:03Z"],["dc.date.issued","2019"],["dc.date.updated","2022-02-09T13:23:16Z"],["dc.description.abstract","The formation of neutrophil extracellular traps (NETs) is an immune defense mechanism of neutrophilic granulocytes. Moreover, it is also involved in the pathogenesis of autoimmune, inflammatory, and neoplastic diseases. For that reason, the process of NET formation (NETosis) is subject of intense ongoing research. In vitro approaches to quantify NET formation are commonly used and involve neutrophil stimulation with various activators such as phorbol 12-myristate 13-acetate (PMA), lipopolysaccharides (LPS), or calcium ionophores (CaI). However, the experimental conditions of these experiments, particularly the media and media supplements employed by different research groups, vary considerably, rendering comparisons of results difficult. Here, we present the first standardized investigation of the influence of different media supplements on NET formation in vitro. The addition of heat-inactivated (hi) fetal calf serum (FCS), 0.5% human serum albumin (HSA), or 0.5% bovine serum albumin (BSA) efficiently prevented NET formation of human neutrophils following stimulation with LPS and CaI, but not after stimulation with PMA. Thus, serum components such as HSA, BSA and hiFCS (at concentrations typically found in the literature) inhibit NET formation to different degrees, depending on the NETosis inducer used. In contrast, in murine neutrophils, NETosis was inhibited by FCS and BSA, regardless of the inducer employed. This shows that mouse and human neutrophils have different susceptibilities toward the inhibition of NETosis by albumin or serum components. Furthermore, we provide experimental evidence that albumin inhibits NETosis by scavenging activators such as LPS. We also put our results into the context of media supplements most commonly used in NET research. In experiments with human neutrophils, either FCS (0.5-10%), heat-inactivated (hiFCS, 0.1-10%) or human serum albumin (HSA, 0.05-2%) was commonly added to the medium. For murine neutrophils, serum-free medium was used in most cases for stimulation with LPS and CaI, reflecting the different sensitivities of human and murine neutrophils to media supplements. Thus, the choice of media supplements greatly determines the outcome of experiments on NET-formation, which must be taken into account in NETosis research."],["dc.identifier.doi","10.3389/fimmu.2019.00012"],["dc.identifier.eissn","1664-3224"],["dc.identifier.pmid","30733715"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15847"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59691"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-3224"],["dc.relation.issn","1664-3224"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Serum and Serum Albumin Inhibit in vitro Formation of Neutrophil Extracellular Traps (NETs)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Immunology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Neubert, Elsa"],["dc.contributor.author","Bach, Katharina Marie"],["dc.contributor.author","Busse, Julia"],["dc.contributor.author","Bogeski, Ivan"],["dc.contributor.author","Schön, Michael P."],["dc.contributor.author","Kruss, Sebastian"],["dc.contributor.author","Erpenbeck, Luise"],["dc.date.accessioned","2020-12-10T18:44:25Z"],["dc.date.available","2020-12-10T18:44:25Z"],["dc.date.issued","2019"],["dc.description.abstract","Neutrophil Extracellular Traps (NETs) are produced by neutrophilic granulocytes and consist of decondensed chromatin decorated with antimicrobial peptides. They defend the organism against intruders and are released upon various stimuli including pathogens, mediators of inflammation, or chemical triggers. NET formation is also involved in inflammatory, cardiovascular, malignant diseases, and autoimmune disorders like rheumatoid arthritis, psoriasis, or systemic lupus erythematosus (SLE). In many autoimmune diseases like SLE or dermatomyositis, light of the ultraviolet-visible (UV-VIS) spectrum is well-known to trigger and aggravate disease severity. However, the underlying connection between NET formation, light exposure, and disease exacerbation remains elusive. We studied the effect of UVA (375 nm), blue (470 nm) and green (565 nm) light on NETosis in human neutrophils ex vivo. Our results show a dose- and wavelength-dependent induction of NETosis. Light-induced NETosis depended on the generation of extracellular reactive oxygen species (ROS) induced by riboflavin excitation and its subsequent reaction with tryptophan. The light-induced NETosis required both neutrophil elastase (NE) as well as myeloperoxidase (MPO) activation and induced histone citrullination. These findings suggest that NET formation as a response to light could be the hitherto missing link between elevated susceptibility to NET formation in autoimmune patients and photosensitivity for example in SLE and dermatomyositis patients. This novel connection could provide a clue for a deeper understanding of light-sensitive diseases in general and for the development of new pharmacological strategies to avoid disease exacerbation upon light exposure."],["dc.identifier.doi","10.3389/fimmu.2019.02428"],["dc.identifier.eissn","1664-3224"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16550"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78445"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-3224"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Blue and Long-Wave Ultraviolet Light Induce in vitro Neutrophil Extracellular Trap (NET) Formation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","3767"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Neubert, Elsa"],["dc.contributor.author","Meyer, Daniel"],["dc.contributor.author","Rocca, Francesco"],["dc.contributor.author","Günay, Gökhan"],["dc.contributor.author","Kwaczala-Tessmann, Anja"],["dc.contributor.author","Grandke, Julia"],["dc.contributor.author","Senger-Sander, Susanne"],["dc.contributor.author","Geisler, Claudia"],["dc.contributor.author","Egner, Alexander"],["dc.contributor.author","Schön, Michael P."],["dc.contributor.author","Erpenbeck, Luise"],["dc.contributor.author","Kruss, Sebastian"],["dc.date.accessioned","2019-07-09T11:45:55Z"],["dc.date.available","2019-07-09T11:45:55Z"],["dc.date.issued","2018"],["dc.description.abstract","Neutrophilic granulocytes are able to release their own DNA as neutrophil extracellular traps (NETs) to capture and eliminate pathogens. DNA expulsion (NETosis) has also been documented for other cells and organisms, thus highlighting the evolutionary conservation of this process. Moreover, dysregulated NETosis has been implicated in many diseases, including cancer and inflammatory disorders. During NETosis, neutrophils undergo dynamic and dramatic alterations of their cellular as well as sub-cellular morphology whose biophysical basis is poorly understood. Here we investigate NETosis in real-time on the single-cell level using fluorescence and atomic force microscopy. Our results show that NETosis is highly organized into three distinct phases with a clear point of no return defined by chromatin status. Entropic chromatin swelling is the major physical driving force that causes cell morphology changes and the rupture of both nuclear envelope and plasma membrane. Through its material properties, chromatin thus directly orchestrates this complex biological process."],["dc.identifier.doi","10.1038/s41467-018-06263-5"],["dc.identifier.pmid","30218080"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15346"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59338"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2041-1723"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Chromatin swelling drives neutrophil extracellular trap release"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2320"],["dc.bibliographiccitation.journal","Frontiers in Immunology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Gruhn, Antonia Luise"],["dc.contributor.author","Kudryasheva, Galina"],["dc.contributor.author","Günay, Gökhan"],["dc.contributor.author","Meyer, Daniel"],["dc.contributor.author","Busse, Julia"],["dc.contributor.author","Neubert, Elsa"],["dc.contributor.author","Erpenbeck, Luise"],["dc.contributor.author","Schön, Michael P."],["dc.contributor.author","Rehfeldt, Florian"],["dc.contributor.author","Kruss, Sebastian"],["dc.date.accessioned","2020-11-18T14:37:03Z"],["dc.date.available","2020-11-18T14:37:03Z"],["dc.date.issued","2019"],["dc.description.abstract","Neutrophils are the most abundant type of white blood cells. Upon stimulation, they are able to decondense and release their chromatin as neutrophil extracellular traps (NETs). This process (NETosis) is part of immune defense mechanisms but also plays an important role in many chronic and inflammatory diseases such as atherosclerosis, rheumatoid arthritis, diabetes, and cancer. For this reason, much effort has been invested into understanding biochemical signaling pathways in NETosis. However, the impact of the mechanical micro-environment and adhesion on NETosis is not well-understood. Here, we studied how adhesion and especially substrate elasticity affect NETosis. We employed polyacrylamide (PAA) gels with distinctly defined elasticities (Young's modulus E) within the physiologically relevant range from 1 to 128 kPa and coated the gels with integrin ligands (collagen I, fibrinogen). Neutrophils were cultured on these substrates and stimulated with potent inducers of NETosis: phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS). Interestingly, PMA-induced NETosis was neither affected by substrate elasticity nor by different integrin ligands. In contrast, for LPS stimulation, NETosis rates increased with increasing substrate elasticity (E > 20 kPa). LPS-induced NETosis increased with increasing cell contact area, while PMA-induced NETosis did not require adhesion at all. Furthermore, inhibition of phosphatidylinositide 3 kinase (PI3K), which is involved in adhesion signaling, completely abolished LPS-induced NETosis but only slightly decreased PMA-induced NETosis. In summary, we show that LPS-induced NETosis depends on adhesion and substrate elasticity while PMA-induced NETosis is completely independent of adhesion."],["dc.identifier.doi","10.3389/fimmu.2019.02320"],["dc.identifier.pmid","31632402"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16478"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/68803"],["dc.language.iso","en"],["dc.notes.intern","DeepGreen Import"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-3224"],["dc.relation.issn","1664-3224"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Effect of Adhesion and Substrate Elasticity on Neutrophil Extracellular Trap Formation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]