Platelet mitochondrial transfer via extracellular vesicles modulates neutrophil phenotype and function

Abstract

Platelet activation causes the release of extracellular vesicles, of which a small proportion contain respiratory competent mitochondria. Mitochondria are integral for energy production and in the regulation of apoptotic pathways. However, the existence of extracellular mitochondria highlights a potential new role in intercellular communication. We hypothesised that platelet extracellular vesicles could be taken up by circulatory cells and alter their function. In this work we demonstrate that platelet extracellular vesicles containing mitochondria interact with and are internalised by neutrophils. Flow cytometry revealed that this interaction promotes neutrophil surface receptor changes, indicative of enhanced neutrophil activation, adhesion and migration pathways. The internalisation of platelet mitochondria renders neutrophils unable to subsequently engulf bacteria, demonstrating reduced phagocytic capacity, but enhances the formation of neutrophil extracellular traps, both alone and in the presence of additional stimuli. Our findings show that platelet mitochondria released in extracellular vesicles can alter neutrophil activity and so may be important intercellular communicators and modulators of inflammatory and immune responses.