Mechanisms of action of naturally occurring antibodies against beta-amyloid on microglia

作者：Gold Maike; Mengel David; Roeskam Stephan; Dodel Richard^*; Bach Jan Philipp

来源：Journal of Neuroinflammation, 2013, 10: 5.

DOI：10.1186/1742-2094-10-5

• Alzheimer%26apos
• s disease
• beta-amyloid
• Microglia
• Inflammation
• Immunoglobulins

Background: Naturally occurring autoantibodies against amyloid-beta (nAbs-A beta) have been shown to exert beneficial effects on transgenic Alzheimer%26apos;s disease (AD) animals in vivo and on primary neurons in vitro. Not much is known about their effect on microglial cells. Our aim was to investigate the effect of nAbs-A beta on amyloid-beta (A beta)-treated microglial cells in vitro with respect to cell viability, stress pathways, cytokine production and phagocytotic abilities and whether these effects can be conveyed to neurons. %26lt;br%26gt;Methods: Primary microglial cells isolated from Swiss Webster mouse mesencephalons on embryonic day 13.5 were pretreated with nAbs-A beta and then treated with A beta oligomers. After 3 hours, phagocytosis as well as western blot analysis were evaluated to measure the amount of phagocytized A beta. Cell viability was analyzed using an MTT assay 24 hours after treatment. Pro-inflammatory cytokines in the supernatants were analyzed with ELISAs and then we treated primary neuronal cells with these conditioned microglia supernatants. Twenty-four hours later we did a MTT assay of the treated neurons. We further investigated the effect of a single nAbs-A beta administration on Tg2576 mice in vivo. %26lt;br%26gt;Results: Upon co-administration of A beta and nAbs-A beta no change in microglia viability was observed. However, there was an increase in phosphorylated p38 protein level, an increase in the pro-inflammatory cytokines TNF-alpha and IL-6 and an increase in A beta uptake by microglial cells. Treatment of primary neurons with conditioned microglia medium led to a 10% improvement in cell viability when nAbs-A beta were co-administered compared to A beta-treated cells alone. We were unable to detect changes in cytokine production in brain lysates of Tg2576 mice. %26lt;br%26gt;Conclusions: We provide evidence on the mechanism of action of nAbs-A beta on microglia in vitro. Interestingly, our in vivo data indicate that nAbs-A beta administration should be considered as a therapeutic strategy in AD, since there is no inflammatory reaction.

• 出版日期2013-1-14