Abstract
Microglial cells are professional phagocytes of the CNS responsible for clearance of unwanted structures. Neuronal processes are marked by complement C1 before they are removed in development or during disease processes. Target molecules involved in C1 binding and mechanisms of clearance are still unclear. Here we show that the terminal sugar residue sialic acid of the mouse neuronal glycocalyx determines complement C1 binding and microglial-mediated clearance function. Several early components of the classical complement cascade including C1q, C1r, C1s, and C3 were produced by cultured mouse microglia. The opsonin C1q was binding to neurites after enzymatic removal of sialic acid residues from the neuronal glycocalyx. Desialylated neurites, but not neurites with intact sialic acid caps, were cleared and taken up by cocultured microglial cells. The removal of the desialylated neurites was mediated via the complement receptor-3 (CR3; CD11b/CD18). Data demonstrate that mouse microglial cells via CR3 recognize and remove neuronal structures with an altered neuronal glycocalyx lacking terminal sialic acid.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Animals, Newborn
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Antigens, CD / metabolism
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Brain / cytology
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CD11b Antigen / metabolism
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Cells, Cultured
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Coculture Techniques
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Complement C1q / metabolism*
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Complement C1q / pharmacology
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Complement C3 / genetics
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Complement C3 / metabolism
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Cytokines / pharmacology
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Embryo, Mammalian
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Female
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Flow Cytometry
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Gene Expression Regulation / drug effects
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Glycocalyx / drug effects
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Glycocalyx / metabolism*
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Green Fluorescent Proteins / genetics
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Humans
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Lipopolysaccharides / pharmacology
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Male
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Mice
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Mice, Inbred C57BL
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Microglia / drug effects
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Microglia / metabolism*
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Neuraminidase / pharmacology
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Neurons / cytology*
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Neurons / drug effects
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Protein Binding / drug effects
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Protein Binding / physiology
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Receptors, Complement / genetics
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Receptors, Complement / metabolism*
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Sialic Acids / metabolism*
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Transfection
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Tubulin / metabolism
Substances
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Antigens, CD
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CD11b Antigen
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Complement C3
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Cytokines
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Lipopolysaccharides
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Receptors, Complement
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Sialic Acids
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Tubulin
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beta3 tubulin, mouse
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Green Fluorescent Proteins
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Complement C1q
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Neuraminidase