| dc.contributor.advisor | Erpenbeck, Luise Dr. | |
| dc.contributor.advisor | Kruss, Sebastian Dr. | |
| dc.contributor.author | Neubert, Elsa | |
| dc.date.accessioned | 2019-12-03T13:05:44Z | |
| dc.date.available | 2020-05-06T22:50:03Z | |
| dc.date.issued | 2019-12-03 | |
| dc.identifier.uri | http://hdl.handle.net/21.11130/00-1735-0000-0005-12BF-0 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-7746 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-7746 | |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 610 | |
| dc.title | Dynamics of Neutrophil Extracellular Trap (NET) Formation | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Schön, Michael P. Prof. Dr. | |
| dc.date.examination | 2019-05-07 | |
| dc.description.abstracteng | Neutrophil granulocytes are the largest group of white blood cells and play a significant role
in the innate immune system. With the discovery of a vast number of thus far unknown
functions, neutrophil granulocytes became a focus in biomedical research. One of the most
remarkable findings are neutrophil extracellular traps (NETs), fibril networks of decondensed
chromatin with attached antimicrobial proteins that can be released as a response to various
stimuli in order to defend pathogens. The process of NET formation (NETosis) is
evolutionarily highly conserved and involved in many pathological conditions. A detailed
analysis of NETosis can, therefore, contribute to a better understanding of such diseases and
therapeutic strategies.
So far, the biophysical forces driving the morphological alternations that underlie chromatin
decondensation and subsequent NET release are poorly understood. This issue is addressed
in the first manuscript of this thesis. The results of this study show that NETosis occurs in
three distinct phases of which only the first depends on enzymatic activity and energy
consumption. The second phase is primarily driven by material properties and entropic
swelling of chromatin. Therefore, the start of chromatin decondensation with nuclear
envelope breakdown (onset of phase 2) represents a point of no return in NETosis. Complete
chromatin decondensation is followed by NET release through rupture of the plasma
membrane at a predetermined breaking point (phase 3). This biophysical characterization
facilitates our understanding of the precise mechanisms of NETosis and highlights the extent
by which complex biological processes can be driven by material properties.
In vitro NETosis studies are being conducted by an ever-increasing number of groups. They
use highly diverse amounts of serum and serum albumin in their culture media. This is
problematic, as these supplements interfere with NETosis depending on their concentration,
used stimulus and neutrophil donor species (human vs. mouse). Details are analyzed in the
second manuscript, which contributes to the comparability of research conditions.
Furthermore, ultraviolet-visible (UV-Vis) light can massively alter cell functions. The third
manuscript investigates the effect of UVA and blue light on NETosis. Light activates a
neutrophil elastase (NE)- and myeloperoxidase (MPO)-dependent pathway of ‘suicidal’
NETosis, which requires the riboflavin-mediated generation of reactive oxygen species
(ROS). External factors, therefore, have a crucial impact on NET formation, which has to be
considered for in vitro studies. Additionally, light-induced NETosis may be of particular
interest in the pathogeneses of light-sensitive disorders (“photodermatoses”) including
autoimmune diseases such as lupus erythematosus.
Together, these studies provide detailed insight into the mechanisms of NET formation and
their regulation. | de |
| dc.contributor.coReferee | Wienands, Jürgen Prof. Dr. | |
| dc.contributor.thirdReferee | Schilling, Bastian Prof. Dr. | |
| dc.subject.eng | Neutrophil extracellular trap (NET) formation | de |
| dc.subject.eng | Neutrophil granulocytes | de |
| dc.subject.eng | Innate immunity | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-21.11130/00-1735-0000-0005-12BF-0-2 | |
| dc.affiliation.institute | Medizinische Fakultät | |
| dc.subject.gokfull | Immunologie / Allergologie / Umweltmedizin / Medizinische Ökologie - Allgemein- und Gesamtdarstellungen (PPN619875445) | de |
| dc.subject.gokfull | Dermatologie / Venerologie - Allgemein- und Gesamtdarstellungen (PPN619876174) | de |
| dc.description.embargoed | 2020-05-06 | |
| dc.identifier.ppn | 1684137519 | |