The implication of microglial sialic acid-binding immunoglobulin-like lectin-E (Siglec-E) in neuroinflammation
The implication of microglial sialic acid-binding immunoglobulin-like lectin-E (Siglec-E) in neuroinflammation
dc.contributor.advisor | Neumann, Harald | |
dc.contributor.author | Claude, Janine | |
dc.date.accessioned | 2020-04-19T19:42:02Z | |
dc.date.available | 2020-04-19T19:42:02Z | |
dc.date.issued | 07.03.2014 | |
dc.identifier.uri | https://hdl.handle.net/20.500.11811/6044 | |
dc.description.abstract | Microglia are the resident immune cells of the central nervous system (CNS). They display a whole set of recognition receptors on their cell surface to sense intact or lesioned cells in the CNS. A subfamily of these receptors are sialic acid-binding immunoglobulin like lectins (Siglecs). Siglecs can either exert activatory or inhibitory signals. Siglec-E is a member of this receptor family and has an immunoreceptor tyrosine based inhibitory motif (ITIM) in the cytoplasmic tail to suppress activatory microglial signals. To study Siglec-E transcription and expression profile ex vivo, primary and stem cell-derived microglia were used. Via RT-PCR and flow cytometry it was shown that Siglec-E is expressed on microglia and was up-regulated following IFN-γ treatment. To study the functional role of Siglec-E, lentiviral knock-down and overexpression of Siglec-E was performed. Lentiviral overexpression of Siglec-E decreased whereas knock-down increased the phagocytosis rate of neural debris and its associated reactive oxygen burst. The extracellular domain of Siglec-E linked to the Fc-part of immunoglobulin bound to the sialic acid residues of the neuronal glycocalyx. Therefore, primary hippocampal neurons were co-cultured with the modified microglia. Overexpression and knock-down of Siglec-E led to an increase and decrease in relative neurite length, respectively. The neuroprotective effect of Siglec E was abrogated after removal of the sialic acid residues on the neuronal glycocalyx. Treatment with the anti-oxidant Trolox abolished the neurotoxic effect of the Siglec-E knock-down on neurite length. In summary, our data suggest an immunomodulatory function of Siglec-E on microglia, which leads to a neuroprotective phenotype by decreasing the production of reactive oxygen species and a reduced phagocytosis rate of neural debris. | |
dc.language.iso | eng | |
dc.rights | In Copyright | |
dc.rights.uri | http://rightsstatements.org/vocab/InC/1.0/ | |
dc.subject | Mikroglia | |
dc.subject | Neuroinflammation | |
dc.subject | Phagozytose | |
dc.subject.ddc | 570 Biowissenschaften, Biologie | |
dc.subject.ddc | 610 Medizin, Gesundheit | |
dc.title | The implication of microglial sialic acid-binding immunoglobulin-like lectin-E (Siglec-E) in neuroinflammation | |
dc.type | Dissertation oder Habilitation | |
dc.publisher.name | Universitäts- und Landesbibliothek Bonn | |
dc.publisher.location | Bonn | |
dc.rights.accessRights | openAccess | |
dc.identifier.urn | https://nbn-resolving.org/urn:nbn:de:hbz:5n-35230 | |
ulbbn.pubtype | Erstveröffentlichung | |
ulbbnediss.affiliation.name | Rheinische Friedrich-Wilhelms-Universität Bonn | |
ulbbnediss.affiliation.location | Bonn | |
ulbbnediss.thesis.level | Dissertation | |
ulbbnediss.dissID | 3523 | |
ulbbnediss.date.accepted | 07.02.2014 | |
ulbbnediss.fakultaet | Mathematisch-Naturwissenschaftliche Fakultät | |
dc.contributor.coReferee | Schultze, Joachim L. |
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