Department of Pathology, UAB Mitochondrial Medicine Laboratory, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Lab Invest. 2013 Jun;93(6):690-700. doi: 10.1038/labinvest.2013.53. Epub 2013 Mar 25.
Peripheral blood mononuclear cells and platelets have long been recognized as having the potential to act as sensitive markers for mitochondrial dysfunction in a broad range of pathological conditions. However, the bioenergetic function of these cells has not been examined from the same donors, yet this is important for the selection of cell types for translational studies. Here, we demonstrate the measurement of cellular bioenergetics in isolated human monocytes, lymphocytes, and platelets, including the oxidative burst from neutrophils and monocytes from individual donors. With the exception of neutrophils, all cell types tested exhibited oxygen consumption that could be ascribed to oxidative phosphorylation with each having a distinct bioenergetic profile and distribution of respiratory chain proteins. In marked contrast, neutrophils were essentially unresponsive to mitochondrial respiratory inhibitors indicating that they have a minimal requirement for oxidative phosphorylation. In monocytes and neutrophils, we demonstrate the stimulation of the oxidative burst using phorbol 12-myristate 13-acetate and its validation in normal human subjects. Taken together, these data suggest that selection of cell type from blood cells is critical for assessing bioenergetic dysfunction and redox biology in translational research.
外周血单核细胞和血小板一直被认为具有作为广泛病理条件下线粒体功能障碍的敏感标志物的潜力。然而，这些细胞的生物能量功能尚未从同一供体进行检查，但这对于转化研究中细胞类型的选择很重要。在这里，我们展示了从个体供体中分离的人单核细胞、淋巴细胞和血小板的细胞生物能量学的测量，包括中性粒细胞和单核细胞的氧化爆发。除了中性粒细胞外，所有测试的细胞类型都表现出可归因于氧化磷酸化的耗氧量，每个细胞类型都具有独特的生物能量特征和呼吸链蛋白分布。相比之下，中性粒细胞对线粒体呼吸抑制剂基本无反应，表明它们对氧化磷酸化的需求极小。在单核细胞和中性粒细胞中，我们使用佛波醇 12-肉豆蔻酸 13-醋酸酯刺激氧化爆发，并在正常人体中验证其效果。综上所述，这些数据表明，从血细胞中选择细胞类型对于评估转化研究中的生物能量功能障碍和氧化还原生物学至关重要。
