title: Tumour necrosis factor alpha-induced neuronal loss is mediated by microglial phagocytosis.
abstract: Tumour necrosis factor-α (TNF-α) is a pro-inflammatory cytokine, expressed in many brain pathologies and associated with neuronal loss. We show here that addition of TNF-α to neuronal-glial co-cultures increases microglial proliferation and phagocytosis, and results in neuronal loss that is prevented by eliminating microglia. Blocking microglial phagocytosis by inhibiting phagocytic vitronectin and P2Y6 receptors, or genetically removing opsonin MFG-E8, prevented TNF-α induced loss of live neurons. Thus TNF-α appears to induce neuronal loss via microglial activation and phagocytosis of neurons, causing neuronal death by phagoptosis.
authors.affiliation: Department of Biochemistry, University of Cambridge, UK; Mouse Biology Unit, European Molecular Biology Laboratory, Italy.
authors.forename: Urte
authors.initials: U
authors.lastname: Neniskyte
authors.affiliation: Department of Biochemistry, University of Cambridge, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Vilalta
authors.affiliation: Department of Biochemistry, University of Cambridge, UK. Electronic address: gcb3@cam.ac.uk.
authors.forename: Guy C
authors.initials: GC
authors.lastname: Brown
mesh_terms: D000818:Animals; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000166:cytology* / Q000187:drug effects*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects*; D051381:Rats; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: Lactadherin; Neurodegeneration; Neuroinflammation; Phagoptosis; Vitronectin receptor