Related Experiment Video

Updated: Jul 3, 2026

In vitro Quantitative Imaging Assay for Phagocytosis of Dead Neuroblastoma Cells by iPSC-Macrophages
09:48

In vitro Quantitative Imaging Assay for Phagocytosis of Dead Neuroblastoma Cells by iPSC-Macrophages

Published on: February 14, 2021

MFG-E8 regulates microglial phagocytosis of apoptotic neurons

Abby D Fuller1, Linda J Van Eldik

  • 1Department of Cell and Molecular Biology, Center for Drug Discovery and Chemical Biology, Northwestern University Feinberg School of Medicine, 303 E Chicago Ave, Chicago, IL 60611, USA.

Journal of Neuroimmune Pharmacology : the Official Journal of the Society on Neuroimmune Pharmacology
|August 2, 2008
PubMed

Insights

Microglia use Milk Fat Globule Factor-E8 (MFG-E8) to clear apoptotic cells in the brain. Dysregulation of MFG-E8 may contribute to neurodegenerative diseases like Alzheimer's.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Phagocytosis by macrophages and microglia is crucial for tissue homeostasis.
  • Milk Fat Globule Factor-E8 (MFG-E8) facilitates the clearance of apoptotic cells in the periphery.
  • The role of MFG-E8 in the brain, specifically by microglia, remains largely unknown.

Purpose of the Study:

  • To investigate the production and function of MFG-E8 by microglia.
  • To determine MFG-E8's role in the recognition and engulfment of apoptotic neuronal cells.
  • To explore the potential involvement of MFG-E8 in neurodegenerative diseases.

Main Methods:

  • Assessed MFG-E8 production in the BV-2 microglial cell line.
  • Examined the interaction between MFG-E8 and apoptotic SY5Y neuroblastoma cells.
  • Utilized a dominant-negative MFG-E8 to inhibit phagocytosis.
  • Analyzed MFG-E8 levels in a mouse model of Alzheimer's disease.

Main Results:

  • BV-2 microglial cells produce and release MFG-E8.
  • Apoptotic cells and fractalkine stimulate MFG-E8 release.
  • MFG-E8 enhances the phagocytosis of apoptotic neuronal cells by microglia.
  • MFG-E8 levels are altered in an Alzheimer's disease mouse model.

Conclusions:

  • Microglia utilize MFG-E8 to clear apoptotic neurons in the brain.
  • MFG-E8-mediated phagocytosis by microglia is essential for neuronal health.
  • Disrupted MFG-E8 function may play a role in the pathogenesis of neurodegenerative diseases.

More Related Videos

Assessing Retinal Microglial Phagocytic Function In Vivo Using a Flow Cytometry-based Assay07:19

Assessing Retinal Microglial Phagocytic Function In Vivo Using a Flow Cytometry-based Assay

Published on: October 18, 2016

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Related Concept Videos

Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...