The effects of functional platelet-derived extracellular mitochondria on the inflammatory phenotype of neutrophils

Abstract

Abstract Unregulated inflammation has been associated with chronic inflammatory auto-immune diseases, such as rheumatoid arthritis, multiple sclerosis and atherosclerosis. Polymorphonuclear neutrophils (PMNL) are amongst the immune cells involved in the acute inflammatory response used to fight bacterial infections. Once activated, PMNL release inflammatory mediators in the extracellular milieu to recruit various immune cells required to fight the invading pathogens. Platelets (PLTs) are also implicated in the body’s inflammatory response. Interestingly, activated PLTs can release fully functional mitochondria in the extracellular milieu. Known as the powerhouse of the cell, the mitochondria share similar characteristics with bacteria. Therefore, we hypothesize that PLTs-derived mitochondria present in the extracellular milieu, acting in a similar way as bacteria, induce a sterile inflammatory response that involves the PMNL. The objective of this study was to investigate the sterile inflammatory response of PMNL caused by the exposure of PLTs-derived extracellular mitochondria. Following the co-incubation of PMNL with various physiological doses of PLTs-derived mitochondria, a characterization of the interaction between PMNL and PLTs-derived mitochondria and an investigation of the inflammatory proprieties of PMNL was performed. We have shown that PLTs-derived mitochondria associate with PMNL, resulting in a 2.47-fold mitochondrial-dependent increase in oxygen consumption. Data also shows that PLTs-derived mitochondria significantly induce the release of PMNL microparticles. The knowledge gained from this study provides insight into the mechanism of sterile inflammation in auto-immune diseases.