|Alleviation of neurotoxicity by microglial human Siglec-11.|
|PMID: 20203208 Owner: NLM Status: MEDLINE|
|Sialic acid-binding Ig superfamily lectins (Siglecs) are members of the Ig superfamily that recognize sialic acid residues of glycoproteins. Siglec-11 is a recently identified human-specific CD33-related Siglec that binds to alpha2,8-linked polysialic acids and is expressed on microglia, the brain resident innate immune cells. Polysialylated neuronal cell adhesion molecule (PSA-NCAM) is a putative ligand of Siglec-11. We observed gene transcription and protein expression of Siglec-11 splice variant 2 in human brain tissue samples by RT-PCR and Western blot analysis. Siglec-11 was detected on microglia in human brain tissue by immunohistochemistry. Human Siglec-11 splice variant 2 was ectopically expressed by a lentiviral vector system in cultured murine microglial cells. Stimulation of Siglec-11 by cross-linking suppressed the lipopolysaccharides (LPS)-induced gene transcription of the proinflammatory mediators interleukin-1beta and nitric oxide synthase-2 in microglia. Furthermore, phagocytosis of apoptotic neuronal material was reduced in Siglec-11 transduced microglia. Expression of PSA-NCAM was detected on microglia and neurons by immunohistochemistry and RT-PCR. Coculture of microglia transduced with Siglec-11 and neurons demonstrated neuroprotective function of Siglec-11. The neuroprotective effect of Siglec-11 was dependent on polysialic acid (PSA) residues on neurons, but independent on PSA on microglia. Thus, data demonstrate that human Siglec-11 ectopically expressed on murine microglia interacts with PSA on neurons, reduces LPS-induced gene transcription of proinflammatory mediators, impairs phagocytosis and alleviates microglial neurotoxicity.|
|Yiner Wang; Harald Neumann|
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|Type: Journal Article; Research Support, Non-U.S. Gov't|
|Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 30 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2010 Mar|
|Created Date: 2010-03-05 Completed Date: 2010-05-05 Revised Date: -|
Medline Journal Info:
|Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States|
|Languages: eng Pagination: 3482-8 Citation Subset: IM|
|Neural Regeneration Group, Institute of Reconstructive Neurobiology, University of Bonn, Bonn, Germany.|
|APA/MLA Format Download EndNote Download BibTex|
Alternative Splicing / genetics
Apoptosis / physiology
Cell Communication / physiology
Cytoprotection / physiology
Encephalitis / genetics, metabolism*, physiopathology
Gliosis / genetics, metabolism*, physiopathology
Inflammation Mediators / metabolism
Lectins / genetics, metabolism*
Lipopolysaccharides / pharmacology
Membrane Proteins / genetics, metabolism*
Mice, Inbred C57BL
Microglia / metabolism*
Nerve Degeneration / genetics, metabolism*, physiopathology
Neural Cell Adhesion Molecule L1 / genetics, metabolism
Neurons / metabolism*
Phagocytosis / drug effects, physiology
Protein Isoforms / genetics, metabolism
RNA, Messenger / metabolism
Sialic Acids / genetics, metabolism
|0/Inflammation Mediators; 0/Lectins; 0/Lipopolysaccharides; 0/Membrane Proteins; 0/Neural Cell Adhesion Molecule L1; 0/Protein Isoforms; 0/RNA, Messenger; 0/SIGLEC11 protein, human; 0/Sialic Acids; 0/polysialic acid; 0/polysialyl neural cell adhesion molecule|
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