Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis (Retracted article. See vol. 19, 2021)
Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis (Retracted article. See vol. 19, 2021)
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DOI：
10.1371/journal.pbio.1002336
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发表时间：
2016-01-01
期刊：
影响因子：
9.8
通讯作者：
Parent, Carole A.
中科院分区：
文献类型：
--
作者：
Majumdar, Ritankar;Tameh, Aidin Tavakoli;Parent, Carole A.
白三烯 B-4 (LTB4) 由趋化性中性粒细胞分泌，形成二级梯度，扩大主要趋化剂的作用范围。这种策略增加了中性粒细胞的募集范围，并且在炎症期间很重要。在这里，我们表明 LTB4 及其合成酶定位于细胞内的多泡体，在刺激后，将其内容物作为外泌体释放。纯化的外泌体可以激活静息中性粒细胞，并以 LTB4 受体依赖性方式引发趋化活性。外泌体释放的抑制会导致定向运动丧失，并伴随 LTB4 释放的丧失。我们的研究结果表明，LTB4 的外泌体库以自分泌方式使中性粒细胞对主要化学引诱剂敏感，并以旁分泌方式介导反式邻近中性粒细胞的募集。我们设想这种机制被其他信号用来促进恶劣的细胞外环境中细胞之间的通信。
Leukotriene B-4 (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 that, upon stimulation, release their content as exosomes. Purified exosomes can activate resting neutrophils and elicit chemotactic activity in a 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.