Open AccessExosomes mediate LTB4 release during neutrophil chemotaxis
Author(s) -
Ritankar Majumdar,
Aidin Tavakoli Tameh,
Subhash B. Arya,
Carole A. Parent
Publication year - 2021
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3001271
Subject(s) - chemotaxis , microbiology and biotechnology , microvesicles , biology , autocrine signalling , paracrine signalling , leukotriene b4 , motility , extracellular , inflammation , intracellular , exosome , stimulation , receptor , immunology , biochemistry , microrna , endocrinology , gene
Leukotriene B 4 (LTB 4 ) 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 LTB 4 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 LTB 4 receptor-dependent manner. Inhibition of exosome release leads to loss of directional motility with concomitant loss of LTB 4 release. Our findings establish that the exosomal pool of LTB 4 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.