Thermal Burn Injury Generates Bioactive Microvesicles: Evidence for a Novel Transport Mechanism for the Lipid Mediator Platelet-Activating Factor (PAF) That Involves Subcellular Particles and the PAF Receptor
Thermal Burn Injury Generates Bioactive Microvesicles: Evidence for a Novel Transport Mechanism for the Lipid Mediator Platelet-Activating Factor (PAF) That Involves Subcellular Particles and the PAF Receptor
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DOI：
10.4049/jimmunol.1901393
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发表时间：
2020-07-01
影响因子：
4.4
通讯作者：
Travers, Jeffrey B.
中科院分区：
文献类型：
--
作者：
Liu, Langni;Fahy, Katherine E.;Travers, Jeffrey B.
热烧伤是一种重要的环境应激源，可导致相当大的发病率和死亡率。环境对皮肤的刺激导致局部和全身影响的确切机制是一个活跃的研究领域。一种允许皮肤角质形成细胞分散生物活性物质的潜在机制是通过微泡颗粒，微泡颗粒是直接从细胞膜释放的亚细胞体。我们以前的研究表明，皮肤角质形成细胞的热烧伤损伤会导致脂质介质血小板激活因子(PAF)的产生。目前的研究表明，热烧伤对体外培养的角质形成细胞、体外培养的人皮肤组织和小鼠体内产生的微泡颗粒均有损伤作用。药理学和遗传学工具的使用表明，微囊的最佳释放取决于PAF受体。值得注意的是，烧伤刺激的微泡颗粒不携带可察觉的蛋白质细胞因子，但含有高水平的PAF。这些研究描述了一种涉及微囊颗粒的新机制，代谢不稳定的生物活性脂质可以通过这种机制从细胞中移动，以响应环境刺激。
Thermal burn injuries are an important environmental stressor that can result in considerable morbidity and mortality. The exact mechanism by which an environmental stimulus to skin results in local and systemic effects is an area of active research. One potential mechanism to allow skin keratinocytes to disperse bioactive substances is via microvesicle particles, which are subcellular bodies released directly from cellular membranes. Our previous studies have indicated that thermal burn injury of the skin keratinocyte in vitro results in the production of the lipid mediator platelet-activating factor (PAF). The present studies demonstrate that thermal burn injury to keratinocytes in vitro and human skin explants ex vivo, and mice in vivo generate microvesicle particles. Use of pharmacologic and genetic tools indicates that the optimal release of microvesicles is dependent upon the PAF receptor. Of note, burn injury-stimulated microvesicle particles do not carry appreciable protein cytokines yet contain high levels of PAF. These studies describe a novel mechanism involving microvesicle particles by which a metabolically labile bioactive lipid can travel from cells in response to environmental stimuli.