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Tumour necrosis factor alpha‐induced neuronal loss is mediated by microglial phagocytosis
Author(s) -
Neniskyte Urte,
Vilalta Anna,
Brown Guy C.
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.05.046
Subject(s) - phagocytosis , microglia , tumor necrosis factor alpha , vitronectin , opsonin , receptor , microbiology and biotechnology , cytokine , necrosis , biology , immunology , neuroscience , chemistry , inflammation , integrin , biochemistry , genetics
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 P2Y 6 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.