Abstract
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 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.
Highlights
After this article [1] was published, the corresponding author noted concerns about some of the reported results
Compared to the primary data, Figs 2A, 2B, 2C, 2G and 3H report images in which dots representing 5-lipoxygenase (5-LO) immunogold signal were added and removed in a manner that supported the article’s hypothesis
Immunogold quantification data in Fig 2F do not provide a true representation of the experimental results
Summary
After this article [1] was published, the corresponding author noted concerns about some of the reported results. The corresponding author agreed with this but commented that the claim about the presence of CD63 on exosomes was supported by other results reported, Fig 3F, and Fig 5A.
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