Effects of Immunomodulatory Substances on Phagocytosis of A𝛽𝟏-𝟒𝟐 by Human Microglia

Abstract

Glial activation and increased inflammation characterize neuropathology in Alzheimer's disease (AD). The aim was to develop a model for studying phagocytosis of 𝛽-amyloid (A𝛽) peptide by human microglia and to test effects thereupon by immunomodulatory substances. Human CHME3 microglia showed intracellular A𝛽1-42 colocalized with lysosome-associated membrane protein-2, indicating phagocytosis. This was increased by interferon-𝛾, and to a lesser degree with Protollin, a proteosome-based adjuvant. Secretion of brain-derived neurotrophic factor (BDNF) was decreased by A𝛽1-42 and by interferon-𝛾 and interleukin-1𝛽. These cytokines, but not A𝛽1-42, stimulated interleukin-6 release. Microglia which phagocytosed A𝛽1-42 exhibited a higher degree of expression of interleukin-1 receptor type I and inducible nitric oxide synthase. In conclusion, we show that human microglia are able to phagocytose A𝛽1-42 and that this is associated with expression of inflammatory markers. A𝛽1-42 and interferon-𝛾 decreased BDNF secretion suggesting a new neuropathological role for A𝛽1-42 and the inflammation accompanying AD.