Exosomes mediate LTB4 release during neutrophil chemotaxis
Ritankar Majumdar, Aidin Tavakoli Tameh, Subhash B. Arya, Carole A. Parent
Abstract
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.