Increased intermediate M1-M2 macrophage polarization and improved cognition in mild cognitive impairment patients on ω-3 supplementation.
Increased intermediate M1-M2 macrophage polarization and improved cognition in mild cognitive impairment patients on ω-3 supplementation.
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DOI：
10.1096/fj.201600677rr
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发表时间：
2017-01
期刊：
影响因子：
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通讯作者：
Fiala M
中科院分区：
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作者：
Famenini S;Rigali EA;Olivera-Perez HM;Dang J;Chang MT;Halder R;Rao RV;Pellegrini M;Porter V;Bredesen D;Fiala M
轻度认知功能障碍（MCI）和阿尔茨海默病（AD）患者的单核/巨噬细胞吞噬和降解淀粉样蛋白β1-42（Aβ1-42）功能缺陷，但ω-3脂肪酸（ω-3s）可改善其功能。本研究假设巨噬细胞主动吞噬Aβ1-42可预防脑淀粉样变性，从而维持认知。我们研究了自我补充ω-3s、抗氧化剂和白藜芦醇饮料对最初诊断为MCI或主观认知障碍（SCI）患者的简易精神状态检查（MMSE）评分、巨噬细胞M1 M2表型[炎症分化簇（CD）54+ CD 80和促消退标记物CD 163 + CD 206的比率]和Aβ1-42吞噬作用的影响。基线时，载脂蛋白E（ApoE）ε3/ε3和ApoE ε3/ε4组患者的中位MMSE评分均为26.0，巨噬细胞Aβ1-42吞噬功能缺陷。ApoE ε3/ε3组的MMSE变化率增加了中位2.2分/年（P = 0.015与0相比），但ApoE ε3/ε4组没有变化（组间P = 0.014）。在ApoE ε3/ε3组中，所有患者的认知保持稳定或改善;在ApoE ε3/ε4组中，1例从痴呆中恢复，但3例陷入痴呆。在携带ApoE ε3/ε3的患者中，巨噬细胞表型以0.226 U/年的速率极化为中间（绿色区）M1-M2型，而在携带ApoE ε3/ε4的患者中，极化为阴性（组间P = 0.08）。在极端M1（红色区域）或M2（白色区域）中的基线M1 M2类型对认知结局不利。两个ApoE组的Aβ1-42吞噬功能均增加（每组P = 0.03）。在体外实验中，ApoE ε3/ε3患者的M1型表达下调，而ε3/ε4患者的M1型表达上调。抗氧化剂/ω-3/白藜芦醇补充与ApoE ε3/ε3和携带ApoE ε3/ε4的个体患者的有利免疫和认知应答相关，并将ω-3介导剂（称为消退素）预期的免疫益处带入个性化临床实践。这项研究的有效性受到其小尺寸和非受控设计的限制。Famenini，S.，Rigali，E.一、Olivera-Perez，H. M.，当，J，Chang，M T.，哈尔德河，拉奥河，巴西-地五、佩莱格里尼，M.，Porter，V.，Bredesen，D.，Fiala，M.补充ω-3可增加中度M1-M2巨噬细胞极化并改善轻度认知障碍患者的认知。
Monocyte/macrophages of patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) are defective in phagocytosis and degradation amyloid β1–42 (Aβ1–42), but are improved by ω-3 fatty acids (ω-3s). The hypothesis of this study was that active Aβ1–42 phagocytosis by macrophages prevents brain amyloidosis and thus maintains cognition. We studied the effects of self-supplementation with a drink with ω-3s, antioxidants, and resveratrol on Mini-Mental State Examination (MMSE) scores, macrophage M1M2 phenotype [the ratio of inflammatory cluster of differentiation (CD)54+CD80 and proresolution markers CD163+CD206], and Aβ1–42 phagocytosis in patients initially diagnosed as having MCI or subjective cognitive impairment (SCI). At baseline, the median MMSE score in patients in both the apolipoprotein E (ApoE) ε3/ε3 and ApoE ε3/ε4 groups was 26.0 and macrophage Aβ1–42 phagocytosis was defective. The MMSE rate of change increased in the ApoE ε3/ε3 group a median 2.2 points per year (P = 0.015 compared to 0) but did not change in the ApoE ε3/ε4 group (P = 0.014 between groups). In the ApoE ε3/ε3 group, all patients remained cognitively stable or improved; in the ApoE ε3/ε4 group, 1 recovered from dementia, but 3 lapsed into dementia. The macrophage phenotype polarized in patients bearing ApoE ε3/ε3 to an intermediate (green zone) M1-M2 type at the rate of 0.226 U/yr, whereas in patients bearing ApoE ε3/ε4, polarization was negative (P = 0.08 between groups). The baseline M1M2 type in the extreme M1 (red zone) or M2 (white zone) was unfavorable for cognitive outcome. Aβ1–42 phagocytosis increased in both ApoE groups (P = 0.03 in each groups). In vitro, the lipidic mediator resolvin D1 (RvD1) down regulated the M1 type in patients with ApoE ε3/ε3 but in some patients with ε3/ε4, paradoxically up-regulated the M1 type. Antioxidant/ω-3/resveratrol supplementation was associated with favorable immune and cognitive responses in ApoE ε3/ε3 and individual patients bearing ApoE ε3/ε4, and brings into personalized clinical practice the immune benefits expected from ω-3 mediators called resolvins. The validity of this study is limited by its small size and uncontrolled design.—Famenini, S., Rigali, E. A., Olivera-Perez, H. M., Dang, J., Chang, M T., Halder, R., Rao, R. V., Pellegrini, M., Porter, V., Bredesen, D., Fiala, M. Increased intermediate M1-M2 macrophage polarization and improved cognition in mild cognitive impairment patients on ω-3 supplementation.