Exosomes mediate LTB4 release during neutrophil chemotaxis

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.
Author’s note Concerns have emerged about the immunoelectron microscopy results originally reported in the article by Majumdar and colleagues [1]. 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 Accordingly, this article has been retracted.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.