Effects of immunomodulatory substances on phagocytosis of abeta(1-42) by human microglia.
Glial activation and increased inflammation characterize neuropathology in Alzheimer's disease (AD). The aim was to develop a model for studying phagocytosis of beta-amyloid (Abeta) peptide by human microglia and to test effects thereupon by immunomodulatory substances. Human CHME3 microglia showed intracellular Abeta(1-42) colocalized with lysosome-associated membrane protein-2, indicating phagocytosis. This was increased by interferon-gamma, and to a lesser degree with Protollin, a proteosome-based adjuvant. Secretion of brain-derived neurotrophic factor (BDNF) was decreased by Abeta(1-42) and by interferon-gamma and interleukin-1beta. These cytokines, but not Abeta(1-42), stimulated interleukin-6 release. Microglia which phagocytosed Abeta(1-42) 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 Abeta(1-42) and that this is associated with expression of inflammatory markers. Abeta(1-42) and interferon-gamma decreased BDNF secretion suggesting a new neuropathological role for Abeta(1-42) and the inflammation accompanying AD.
Hjorth
Erik
E
Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 141 86 Stockholm, Sweden.
Frenkel
Dan
D
Weiner
Howard
H
Schultzberg
Marianne
M
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