Platelet-Derived Microvesicles Modulate the Bioenergetic and Inflammatory Phenotype of Human Polymorphonuclear Leukocytes.

Platelets release microvesicles (PMVs) into the extracellular milieu upon activation. PMVs retain various platelet components, including functional mitochondria, and actively participate in intercellular communication with immune cells such as polymorphonuclear leukocytes (PMN). PMVs have been known to modulate the inflammatory response of PMN under normal physiological condition. Despite growing interest in the transfer of biological material between immune cells, the mitochondrial content shuttling from PMVs to PMN and the resulting effects have remained unclear. Using freshly isolated PMVs from healthy and consenting donors, we demonstrate that PMVs modulate both the bioenergetic and the inflammatory phenotype of the recipient immune cell. We first confirmed the mitochondrial content transfer, and then measured cell viability, mitochondrial respiration, and ATP production. Platelet-derived mitochondria were found associated with PMN, consequently decreasing caspase-3 activity. PMVs increased mitochondrial activity and ATP levels in the recipient cell. Incubation of PMN with PMVs containing non-functional mitochondria did not affect respiration and caspase-3 activity. This demonstrates that functional and active mitochondria are required for the PMVs to modulate the bioenergenetic phenotype of human polymorphonuclear leukocytes. Finally, we detected the transfer of active 12-lipoxygenase and of cyclooxygenase-1 in the recipient cells, enzymes found specifically in PMVs, and an increase in the production of their respective inflammatory products. These findings suggest that platelet-derived mitochondria play a key role in enhancing the survival and inflammatory function of PMN in inflammatory conditions.