Document Detail


Alleviation of neurotoxicity by microglial human Siglec-11.
MedLine Citation:
PMID:  20203208     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Yiner Wang; Harald Neumann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
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 
Date Detail:
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    
Other Details:
Languages:  eng     Pagination:  3482-8     Citation Subset:  IM    
Affiliation:
Neural Regeneration Group, Institute of Reconstructive Neurobiology, University of Bonn, Bonn, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Alternative Splicing / genetics
Animals
Apoptosis / physiology
Cell Communication / physiology
Cells, Cultured
Child
Coculture Techniques
Cytoprotection / physiology
Encephalitis / genetics,  metabolism*,  physiopathology
Female
Genetic Vectors
Gliosis / genetics,  metabolism*,  physiopathology
Humans
Inflammation Mediators / metabolism
Lectins / genetics,  metabolism*
Lipopolysaccharides / pharmacology
Male
Membrane Proteins / genetics,  metabolism*
Mice
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
Transfection
Young Adult
Chemical
Reg. No./Substance:
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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