The implication of microglial sialic acid-binding immunoglobulin-like lectin-E (Siglec-E) in neuroinflammation
Year: 2014
Type: dissertation
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.
Source: bonndoc (University of Bonn)
Author: Claude, Janine
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W6982447095