Functional platelet‐derived mitochondria induce the release of human neutrophil microvesicles

Inflammation is an essential process of host defense against infections, illness, or tissue damage. Polymorphonuclear neutrophils (PMN) are among the first immune cells involved in acute inflammatory responses and are on the front line in the fight against bacterial infections. In the presence of bacterial fragments, PMN release inflammatory mediators, enzymes, and microvesicles in the extracellular milieu to recruit additional immune cells required to eliminate the pathogens. Recent evidence shows that platelets (PLTs), initially described for their role in coagulation, are involved in inflammatory responses. Furthermore, upon activation, PLT also release functional mitochondria (freeMitos) within their extracellular milieu. Mitochondria share characteristics with bacterial and mitochondrial damage‐associated molecular patterns, which are important contributors in sterile inflammation processes. Deep sequencing transcriptome analysis demonstrates that freeMitos increase the mitochondrial gene expression in PMN. However, freeMitos do not affect the mitochondrial‐dependent increase in oxygen consumption in PMN. Interestingly, freeMitos significantly induce the release of PMN‐derived microvesicles. This study provides new insight into the role of freeMitos in the context of sterile inflammation. Synopsis Mitochondria are better appreciated for their role in bioenergy production; however, they are active participants in sterile inflammation. This study reports the transcriptomic profile of human neutrophils modulated by extracellular mitochondria (freeMitos) Platelet‐derived freeMitos increase the expression of several mitochondrial genes in human neutrophils. FreeMitos uptake by neutrophils does not affect cellular respiration in the recipient cell. FreeMitos induce the release of intracellular calcium in neutrophils. Calcium release activates the calpain pathway, triggering the release of neutrophil‐derived microvesicles. Graphical Abstract Mitochondria are better appreciated for their role in bioenergy production; however, they are active participants in sterile inflammation. This study reports the transcriptomic profile of human neutrophils modulated by extracellular mitochondria (freeMitos).