Criticality of plasma membrane lipids reflects activation state of macrophage cells

Criticality of plasma membrane lipids reflects activation state of macrophage cells
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质膜脂质的临界程度反映了巨噬细胞的激活状态

DOI:
10.1101/680157
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发表时间:
2019
期刊:
--
影响因子:
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通讯作者:
Cammarota E
Cammarota E
中科院分区:
--
文献类型:
--
作者:
Cammarota E

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信号传导在免疫细胞中特别重要,并且在信号传导途径的上游,许多膜受体仅作为复合物起作用,与特定的脂质物质共定位。过去15年的工作表明,质膜脂质组成接近相分离的临界点,有证据表明细胞以改变接近该热力学点的方式调整其组成。巨噬细胞是先天免疫系统的关键组成部分,对感染有反应并调节炎症的局部状态。我们调查的变化,质膜的接近临界点作为一个响应刺激的各种促炎剂和抗炎剂。促炎性(干扰素γ、Kdo 2-脂质A、脂多糖)扰动诱导巨质膜囊泡转变温度升高;抗炎性白细胞介素4具有相反的作用。这些变化概括了复杂的质膜组成的变化,并与发挥主要调节作用的脂质临界性一致:接近临界条件增加膜蛋白活性。
Signalling is of particular importance in immune cells, and upstream in the signalling pathway many membrane receptors are functional only as complexes, co-locating with particular lipid species. Work over the last 15 years has shown that plasma membrane lipid composition is close to a critical point of phase separation, with evidence that cells adapt their composition in ways that alter the proximity to this thermodynamic point. Macrophage cells are a key component of the innate immune system, are responsive to infections and regulate the local state of inflammation. We investigate changes in the plasma membrane’s proximity to the critical point as a response to stimulation by various pro- and anti-inflammatory agents. Pro-inflammatory (interferonγ, Kdo 2-Lipid A, lipopolysaccharide) perturbations induce an increase in the transition temperature of giant plasma membrane vesicles; anti-inflammatory interleukin 4 has the opposite effect. These changes recapitulate complex plasma membrane composition changes, and are consistent with lipid criticality playing a master regulatory role: being closer to critical conditions increases membrane protein activity.
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