Platelet-Derived Microvesicles Modulate the Bioenergetic and Inflammatory Phenotype of Human Neutrophils 2192

Abstract Description Platelets release microvesicles (PMVs) upon activation which retain platelet cargo, including functional mitochondria, and actively participate in intercellular communication. Neutrophils (PMN) play a vital role in the innate immune response and inflammation. Despite growing interest in the transfer of biological material between immune cells, the transfer of mitochondrial content from PMVs to PMN and its resulting effects remain unclear. This study aimed to address this gap in literature by investigating if the increase of mitochondria in PMN could delay cell death and prolong the inflammatory response. We show that PMV mitochondria were found associated with PMN, consequently increasing viability. PMVs induced an increase in ATP production, ETS state and mitochondrial reductase activity in the recipient cell. To confirm the implication of platelet-derived mitochondria in the observed changes of the PMN’s phenotype, PMVs were subjected to freeze-thaw cycles to generate dysfunctional mitochondria which did not affect the cellular respiration of PMN or the mitochondrial reductase activity. Interestingly, dysfunctional PMVs showed significantly more caspase-3 activity in PMN compared to fresh PMVs. Finally, we detected the transfer of active 12-lipoxygenase and cyclooxygenase-1 in the PMN, enzymes found specifically in PMVs. These findings suggest that PMV-derived mitochondria play a key role in enhancing the survival and inflammatory function of PMN in inflammatory conditions. Funding Sources Supported by Research New Brunswick and the Canadian Institutes of Health Research. Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)