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The implication of microglial sialic acid-binding immunoglobulin-like lectin-E (Siglec-E) in neuroinflammation

dc.contributor.advisorNeumann, Harald
dc.contributor.authorClaude, Janine
dc.date.accessioned2020-04-19T19:42:02Z
dc.date.available2020-04-19T19:42:02Z
dc.date.issued07.03.2014
dc.identifier.urihttps://hdl.handle.net/20.500.11811/6044
dc.description.abstractMicroglia 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.isoeng
dc.rightsIn Copyright
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectMikroglia
dc.subjectNeuroinflammation
dc.subjectPhagozytose
dc.subject.ddc570 Biowissenschaften, Biologie
dc.subject.ddc610 Medizin, Gesundheit
dc.titleThe implication of microglial sialic acid-binding immunoglobulin-like lectin-E (Siglec-E) in neuroinflammation
dc.typeDissertation oder Habilitation
dc.publisher.nameUniversitäts- und Landesbibliothek Bonn
dc.publisher.locationBonn
dc.rights.accessRightsopenAccess
dc.identifier.urnhttps://nbn-resolving.org/urn:nbn:de:hbz:5n-35230
ulbbn.pubtypeErstveröffentlichung
ulbbnediss.affiliation.nameRheinische Friedrich-Wilhelms-Universität Bonn
ulbbnediss.affiliation.locationBonn
ulbbnediss.thesis.levelDissertation
ulbbnediss.dissID3523
ulbbnediss.date.accepted07.02.2014
ulbbnediss.fakultaetMathematisch-Naturwissenschaftliche Fakultät
dc.contributor.coRefereeSchultze, Joachim L.


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