Microglial CD33-related Siglec-E inhibits neurotoxicity by preventing the phagocytosis-associated oxidative burst.
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.
Neural Regeneration Group, Institute of Reconstructive Neurobiology and Division of Neurochemistry, Department of Epileptology, University of Bonn Medical Center, 53127 Bonn, Germany.
Janine
J
Claude
Bettina
B
Linnartz-Gerlach
Alexei P
AP
Kudin
Wolfram S
WS
Kunz
Harald
H
Neumann
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D016897:Respiratory Burst / Q000502:physiology*; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000096:biosynthesis*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C571165:Cd33 protein, mouse; D018696:Neuroprotective Agents; D063268:Sialic Acid Binding Ig-like Lectin 3; C422908:Siglece protein, mouse