Interdisciplinary Post-graduate Program in Health Sciences, Cruzeiro of Sul University, Sao Paulo, Sao Paulo, Brazil,
Interdisciplinary Post-graduate Program in Health Sciences, Cruzeiro of Sul University, Sao Paulo, Sao Paulo, Brazil.
Cell Physiol Biochem. 2020 Jun 27;54(4):629-647. doi: 10.33594/000000245.
Neutrophils were traditionally considered as short-lived cells with abundant secretory and protein synthetic activity. Recent studies, however, indicate neutrophils are in reality a heterogeneous population of cells. Neutrophils differentiate from pluripotent stem cells in the bone marrow, and can further mature in the blood stream and can have different phenotypes in health and disease conditions. Neutrophils undergo primary functions such as phagocytosis, production of reactive oxygen species (ROS), release of lipid mediators and inflammatory proteins (mainly cytokines), and apoptosis. Neutrophils stimulate other neutrophils and trigger a cascade of immune and inflammatory responses. The underpinning intracellular metabolisms that support these neutrophil functions are herein reported. It has been known for many decades that neutrophils utilize glucose as a primary fuel and produce lactate as an end product of glycolysis. Neutrophils metabolize glucose through glycolysis and the pentose- phosphate pathway (PPP). Mitochondrial glucose oxidation is very low. The PPP provides the reduced nicotinamide adenine dinucleotide phosphate (NADPH) for the NADPH-oxidase (NOX) complex activity to produce superoxide from oxygen. These cells also utilize glutamine and fatty acids to produce the required adenosine triphosphate (ATP) and precursors for the synthesis of molecules that trigger functional outcomes. Neutrophils obtained from rat intraperitoneal cavity and incubate for 1 hour at 37°C metabolize glutamine at higher rate than that of glucose. Glutamine delays neutrophil apoptosis and maintains optimal NOX activity for superoxide production. Under limited glucose provision, neutrophils move to fatty acid oxidation (FAO) to obtain the required energy for the cell function. FAO is mainly associated with neutrophil differentiation and maturation. Hypoxia, hormonal dysfunction, and physical exercise markedly change neutrophil metabolism. It is now become clear that neutrophil metabolism underlies the heterogeneity of neutrophil phenotypes and should be intense focus of investigation.
中性粒细胞传统上被认为是寿命短、分泌和蛋白质合成活性丰富的细胞。然而，最近的研究表明，中性粒细胞实际上是一个异质性的细胞群体。中性粒细胞从骨髓中的多能干细胞分化而来，并可在血液中进一步成熟，并在健康和疾病状态下具有不同的表型。中性粒细胞发挥吞噬作用、产生活性氧物质 (ROS)、释放脂质介质和炎症蛋白（主要是细胞因子）以及凋亡等主要功能。中性粒细胞刺激其他中性粒细胞并引发一系列免疫和炎症反应。本文报告了支持这些中性粒细胞功能的潜在细胞内代谢。几十年来，人们一直知道中性粒细胞将葡萄糖作为主要燃料，并将乳酸作为糖酵解的终产物。中性粒细胞通过糖酵解和戊糖磷酸途径 (PPP) 代谢葡萄糖。线粒体葡萄糖氧化非常低。PPP 为 NADPH 氧化酶 (NOX) 复合物的活性提供还原型烟酰胺腺嘌呤二核苷酸磷酸 (NADPH)，以将氧气转化为超氧化物。这些细胞还利用谷氨酰胺和脂肪酸来产生所需的三磷酸腺苷 (ATP) 和触发功能结果的分子合成前体。在 37°C 下孵育 1 小时从大鼠腹腔中获得的中性粒细胞以比葡萄糖更高的速率代谢谷氨酰胺。谷氨酰胺可延迟中性粒细胞凋亡并维持产生超氧化物的最佳 NOX 活性。在葡萄糖供应有限的情况下，中性粒细胞会转向脂肪酸氧化 (FAO) 以获得细胞功能所需的能量。FAO 主要与中性粒细胞分化和成熟有关。缺氧、激素功能障碍和体育锻炼会显著改变中性粒细胞的代谢。现在已经清楚，中性粒细胞代谢是中性粒细胞表型异质性的基础，应该成为研究的重点。
