Lipid body accumulation alters calcium signaling dynamics in immune cells.
Lipid body accumulation alters calcium signaling dynamics in immune cells.
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DOI：
10.1016/j.ceca.2014.06.004
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发表时间：
2014-09
期刊：
影响因子：
4
通讯作者：
Turner H
中科院分区：
文献类型：
--
作者：
Greineisen WE;Speck M;Shimoda LM;Sung C;Phan N;Maaetoft-Udsen K;Stokes AJ;Turner H
巨噬细胞、嗜酸性粒细胞和中性粒细胞中脂质体（LB）的数量存在明确的变异性。类似于在高胰岛素血症和营养物过载期间在脂肪细胞和肝细胞中观察到的脂肪变性，免疫细胞LB响应于细菌和寄生虫感染和炎症呈现而过度积累。最近，我们描述了高胰岛素血症，在体外和体内，驱动脂肪变性和表型变化的主要和转化肥大细胞和嗜碱性粒细胞。LB在这些脂肪变性的细胞质中达到很高的数量，在这里，我们提出，它们可能会显着影响跨胞质信号通路。我们比较了正常和脂肪变性模型肥大细胞在群体和单个细胞水平上的钙释放和内流反应。在群体水平，Fcε RI依赖性钙动员的所有方面以及钙依赖性下游信号传导靶点（如NFATC 1磷酸化）的激活均受到抑制。在单细胞水平，我们证明LB是FcεRI交联后钙的来源和汇。LB的存在对跨细胞质钙信号的速率的影响的无偏分析表明，LB富集加速钙传播，这可能反映了伯努利效应。因此，LB丰度影响这一基本信号传导途径及其下游靶标。
There is well-established variability in the numbers of lipid bodies (LB) in macrophages, eosinophils, and neutrophils. Similarly to the steatosis observed in adipocytes and hepatocytes during hyperinsulinemia and nutrient overload, immune cell LB hyper-accumulate in response to bacterial and parasitic infection and inflammatory presentations. Recently we described that hyperinsulinemia, both in vitro and in vivo, drives steatosis and phenotypic changes in primary and transformed mast cells and basophils. LB reach high numbers in these steatotic cytosols, and here we propose that they could dramatically impact the transcytoplasmic signaling pathways. We compared calcium release and influx responses at the population and single cell level in normal and steatotic model mast cells. At the population level, all aspects of FcεRI-dependent calcium mobilization, as well as activation of calcium-dependent downstream signalling targets such as NFATC1 phosphorylation are suppressed. At the single cell level, we demonstrate that LB are both sources and sinks of calcium following FcεRI cross-linking. Unbiased analysis of the impact of the presence of LB on the rate of trans-cytoplasmic calcium signals suggest that LB enrichment accelerates calcium propagation, which may reflect a Bernoulli effect. LB abundance thus impacts this fundamental signalling pathway and its downstream targets.
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影响因子：
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作者：
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通讯作者：
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DOI：
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发表时间：
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影响因子：
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通讯作者：
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