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Updated: May 24, 2026
In vitro Quantitative Imaging Assay for Phagocytosis of Dead Neuroblastoma Cells by iPSC-Macrophages
Published on: February 14, 2021
MFG-E8 mediates primary phagocytosis of viable neurons during neuroinflammation
Michael Fricker1, Jonas J Neher, Jing-Wei Zhao
1Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK.
Abstract:
Milk-fat globule EGF factor-8 (MFG-E8, SED1, lactadherin) is known to mediate the phagocytic removal of apoptotic cells by bridging phosphatidylserine (PS)-exposing cells and the vitronectin receptor (VR) on phagocytes. However, we show here that MFG-E8 can mediate phagocytosis of viable neurons during neuroinflammation induced by lipopolysaccharide (LPS), thereby causing neuronal death. In vitro, inflammatory neuronal loss is independent of apoptotic pathways, and is inhibited by blocking the PS/MFG-E8/VR pathway (by adding PS blocking antibodies, annexin V, mutant MFG-E8 unable to bind VR, or VR antagonist). Neuronal loss is absent in Mfge8 knock-out cultures, but restored by adding recombinant MFG-E8, without affecting inflammation. In vivo, LPS-induced neuronal loss is reduced in the striatum of Mfge8 knock-out mice or by coinjection of an MFG-E8 receptor (VR) inhibitor into the rat striatum. Our data show that blocking MFG-E8-dependent phagocytosis preserves live neurons, implying that phagocytosis actively contributes to neuronal death during brain inflammation.
Insights
Milk-fat globule EGF factor-8 (MFG-E8) actively causes neuron death during brain inflammation by mediating phagocytosis of viable neurons. Blocking this MFG-E8 pathway preserves neurons, revealing phagocytosis
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Milk-fat globule EGF factor-8 (MFG-E8) typically clears apoptotic cells.
- MFG-E8 bridges phosphatidylserine (PS)-exposing cells and the vitronectin receptor (VR) on phagocytes.
Purpose of the Study:
- To investigate MFG-E8's role in neuronal death during neuroinflammation.
- To determine if MFG-E8 mediates phagocytosis of viable neurons.
Main Methods:
- In vitro studies using neuronal cultures treated with lipopolysaccharide (LPS).
- In vivo studies in Mfge8 knock-out mice and rats.
- Pharmacological inhibition of the PS/MFG-E8/VR pathway.
Main Results:
- MFG-E8 mediates phagocytosis of viable neurons during LPS-induced neuroinflammation.
- Neuronal loss is independent of apoptosis and is inhibited by blocking the PS/MFG-E8/VR pathway.
- Mfge8 knock-out or VR inhibition reduces LPS-induced neuronal death in vivo.
Conclusions:
- MFG-E8 actively contributes to neuronal death by promoting phagocytosis of live neurons.
- Blocking MFG-E8-dependent phagocytosis protects neurons during brain inflammation.
- This pathway represents a potential therapeutic target for neuroinflammatory conditions.
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