Microglial cells kill prion-damaged neurons in vitro by a CD14-dependent process.
Microglial cells killed primary cortical neurons exposed to the prion (PrP)-derived peptide HuPrP106-126. The survival of HuPrP106-126-damaged neurons was increased by pre-treating microglial cells with anti-CD14 antibodies, while microglial cells from CD14 knockout mice failed to kill HuPrP106-126-damaged neurons. In addition, HuPrP106-126-damaged neurons selectively bound a CD14-IgG chimera. The killing of HuPrP106-126-damaged neurons by human monocytes was epitope specific; it was reduced by pre-treating monocytes with some anti-CD14 monoclonal antibodies (mabs) (60bca, 3C10 or MAB3832), but not others (26ic or MAB3831). None of the mabs affected the survival of HuPrP106-126-damaged neurons in the absence of monocytes.
Bate
Clive
C
Department of Pathology and Infectious Diseases, Royal Veterinary College, Hawkshead Lane, North Mymms, Herts AL9 7TA, UK. cbate@rvc.ac.uk
Boshuizen
Ronald
R
Williams
Alun
A
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016923:Cell Death; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D018920:Coculture Techniques; D018604:Epitope Mapping; D000939:Epitopes; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000502:physiology*; D009000:Monocytes / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D011328:Prions / Q000494:pharmacology / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007074:Immunoglobulin G; D018950:Lipopolysaccharide Receptors; D010446:Peptide Fragments; D011328:Prions; D011993:Recombinant Fusion Proteins; C082632:prion protein (106-126)