Microglia kill amyloid-beta1-42 damaged neurons by a CD14-dependent process.
Activated microglia are closely associated with neuronal damage in Alzheimer's disease. In the present study, neurons exposed to low concentrations of amyloid-beta1-42, a toxic fragment of the amyloid-beta protein, were killed by microglia in a process that required cell-cell contact. Pre-treating microglia with polyclonal antibodies to the CD14 protein, or treating neurons exposed to amyloid-beta1-42 with a CD14-IgG chimera, prevented the killing of amyloid-beta1-42 damaged neurons by microglia. Moreover, microglia from CD14 null mice failed to kill amyloid-beta1-42 damaged neurons. Increased neuronal survival was accompanied by a significant reduction in the production of interleukin-6 indicative of reduced microglial activation. These results indicate an important role for CD14 in the recognition and subsequent killing of amyloid-beta damaged neurons by microglia.
Bate
Clive
C
Institute of Comparative Medicine, Department of Veterinary Pathology, Glasgow University Veterinary School, Bearsden Road, Glasgow G61 1QH, UK. c.bate@vet.gla.ac.uk
Veerhuis
Robert
R
Eikelenboom
Piet
P
Williams
Alun
A
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D007074:Immunoglobulin G / Q000235:genetics / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000166:cytology* / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D007074:Immunoglobulin G; D018950:Lipopolysaccharide Receptors; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C075222:amyloid beta-protein (1-42)