Microglial CD33-related Siglec-E inhibits neurotoxicity by preventing the phagocytosis-associated oxidative burst

J Neurosci. 2013 Nov 13;33(46):18270-6. doi: 10.1523/JNEUROSCI.2211-13.2013.


Sialic acid-binding Ig-like lectins (Siglecs) are members of the Ig superfamily that recognize sialic acid residues of glycoproteins. Siglec-E is a mouse CD33-related Siglec that preferentially binds to sialic acid residues of the cellular glycocalyx. Here, we demonstrate gene transcription and protein expression of Siglec-E by cultured mouse microglia. Siglec-E on microglia inhibited phagocytosis of neural debris and prevented the production of superoxide radicals induced by challenge with neural debris. Soluble extracellular Siglec-E receptor protein bound to the neural glycocalyx. Coculture of mouse microglia and neurons demonstrated a neuroprotective effect of microglial Siglec-E that was dependent on neuronal sialic acid residues. Increased neurotoxicity of microglia after knockdown of Siglece mRNA was neutralized by the reactive oxygen species scavenger Trolox. Data suggest that Siglec-E recognizes the intact neuronal glycocalyx and has neuroprotective function by preventing phagocytosis and the associated oxidative burst.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, Differentiation, B-Lymphocyte / biosynthesis
  • Cells, Cultured
  • Coculture Techniques
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / metabolism*
  • Neurons / metabolism*
  • Neuroprotective Agents / metabolism
  • Phagocytosis / physiology*
  • Protein Binding / physiology
  • Respiratory Burst / physiology*
  • Sialic Acid Binding Ig-like Lectin 3 / biosynthesis*


  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • Cd33 protein, mouse
  • Neuroprotective Agents
  • Sialic Acid Binding Ig-like Lectin 3
  • Siglece protein, mouse