Journal
PLOS BIOLOGY
Volume 19, Issue 7, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.3001271
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Funding
- Intramural Research Program of the Center for Cancer Research, NCI, National Institutes of Health [R01AI152517]
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LTB4 is synthesized in multivesicular bodies and released via exosomes to activate neutrophil chemotactic activity. Inhibition of exosome release results in loss of LTB4 release, affecting neutrophil motility and recruitment.
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, 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.
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