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.