Exosomes mediate LTB4 release during neutrophil chemotaxis.
Exosomes mediate LTB4 release during neutrophil chemotaxis.
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DOI：
10.1371/journal.pbio.3001271
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发表时间：
2021-07
期刊：
影响因子：
9.8
通讯作者：
Parent CA
中科院分区：
文献类型：
--
作者：
Majumdar R;Tavakoli Tameh A;Arya SB;Parent CA
白三烯B4(LTB4)由趋化中性粒细胞分泌，形成二次梯度，扩大主要趋化物质的作用范围。这一策略增加了中性粒细胞的募集范围，在炎症期间很重要。在这里，我们展示了LTB4及其合成酶定位于细胞内的多泡小体，这些小体在刺激下以外体的形式释放其内容。纯化的外切体可以激活静息的中性粒细胞，并以LTB4受体依赖的方式诱导趋化活性。抑制外切体的释放会导致失去定向运动性，并伴随着LTB4释放的丧失。我们的发现表明，LTB4的外体池以自分泌的方式使中性粒细胞对主要的趋化物质敏感，并以旁分泌的方式调节邻近的中性粒细胞以反式方式募集。我们设想，这种机制将被其他信号用来促进严酷的细胞外环境中细胞之间的通信。人们对Majudar和他的同事最初在文章中报道的免疫电子显微镜结果表示担忧。此外，在同一文章的图2H和图3D中报告的标尺中也有错误。因此，这篇文章已被撤回。我们非常感谢有机会重新出版这篇文章的一个版本，其中的电子显微镜数据已被删除。删除有争议的数据不会影响原文章中得出的任何主要结论。我们对此事件向PLOS生物学和整个科学界致以诚挚的歉意。
Leukotriene B4 (LTB4) is secreted by chemotactic neutrophils, forming a secondary gradient that amplifies the reach of primary chemoattractants. This strategy increases the recruitment range for neutrophils and is important during inflammation. Here, we show that LTB4 and its synthesizing enzymes localize to intracellular multivesicular bodies, which, upon stimulation, release their content as exosomes. Purified exosomes can activate resting neutrophils and elicit chemotactic activity in an LTB4 receptor-dependent manner. Inhibition of exosome release leads to loss of directional motility with concomitant loss of LTB4 release. Our findings establish that the exosomal pool of LTB4 acts in an autocrine fashion to sensitize neutrophils towards the primary chemoattractant, and in a paracrine fashion to mediate the recruitment of neighboring neutrophils in trans. We envision that this mechanism is used by other signals to foster communication between cells in harsh extracellular environments. Concerns have emerged about the immunoelectron microscopy results originally reported in the article by Majumdar and colleagues. In addition, errors were made in the scale bars reported in Figs 2H and 3D of the same article. Accordingly, this article has been retracted. We are grateful for the opportunity to republish a version of this article in which the electron microscopy data have been removed. None of the major conclusions attained in the original article are affected by the removal of the contentious data. We sincerely apologize to PLOS Biology and the scientific community at large for this occurrence.
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