Department of Pathology and Biomedical Science, University of Otago, Christchurch, P.O. Box 4345, Christchurch 8140, New Zealand.
Nutrients. 2019 Jun 17;11(6):1363. doi: 10.3390/nu11061363.
Vitamin C (ascorbate) is important for neutrophil function and immune health. Studies showing improved immune function have primarily used cells from scorbutic animals or from individuals with infectious conditions or immune cell disorders. Few studies have focused on the requirements of neutrophils from healthy adults. Therefore, we have investigated the role of vitamin C, at concentrations equivalent to those obtained in plasma from oral intakes (i.e., 50-200 µmol/L), on key functions of neutrophils isolated from healthy individuals. Cells were either pre-loaded with dehydroascorbic acid, which is rapidly reduced intracellularly to ascorbate, or the cells were activated in the presence of extracellular ascorbate. We measured the effects of enhanced ascorbate uptake on the essential functions of chemotaxis, oxidant production, programmed cell death and neutrophil extracellular trap (NET) formation. We found that neutrophils isolated from healthy individuals already had replete ascorbate status (0.35 nmol/10 cells), therefore they did not uptake additional ascorbate. However, they readily took up dehydroascorbic acid, thus significantly increasing their intracellular ascorbate concentrations, although this was found to have no additional effect on superoxide production or chemotaxis. Interestingly, extracellular ascorbate appeared to enhance directional mobilityin the presence of the chemoattractant formyl-methionyl-leucyl-phenylalanine (fMLP). Stimulation of the cells in the presence of ascorbate significantly increased intracellular ascorbate concentrations and, although this exhibited a non-significant increase in phosphatidylserine exposure, NET formation was significantly attenuated. Our findings demonstrate the ability of neutrophils to regulate their uptake of ascorbate from the plasma of healthy humans to maintain an optimal level within the cell for proper functioning. Higher oral intakes, however, may help reduce tissue damage and inflammatory pathologies associated with NET formation.
维生素 C（抗坏血酸）对中性粒细胞功能和免疫健康很重要。表明免疫功能改善的研究主要使用来自坏血病动物或患有感染性疾病或免疫细胞疾病个体的细胞。很少有研究关注来自健康成年人的中性粒细胞的需求。因此，我们研究了维生素 C 的作用，其浓度相当于从口服摄入获得的血浆浓度（即 50-200µmol/L），对从健康个体中分离的中性粒细胞的关键功能的影响。细胞要么预先加载脱氢抗坏血酸，其在细胞内迅速还原为抗坏血酸，要么在细胞外抗坏血酸存在下激活细胞。我们测量了增强的抗坏血酸摄取对趋化性、氧化剂产生、程序性细胞死亡和中性粒细胞胞外陷阱（NET）形成等基本功能的影响。我们发现，从健康个体中分离的中性粒细胞已经具有充足的抗坏血酸状态（0.35 nmol/10 个细胞），因此它们不会摄取额外的抗坏血酸。然而，它们很容易摄取脱氢抗坏血酸，从而显著增加其细胞内抗坏血酸浓度，尽管这发现对超氧化物产生或趋化性没有额外的影响。有趣的是，细胞外抗坏血酸似乎在存在趋化因子甲酰基-甲硫氨酸-亮氨酸-苯丙氨酸（fMLP）的情况下增强定向迁移能力。在抗坏血酸存在下刺激细胞显著增加细胞内抗坏血酸浓度，尽管这表现出磷脂酰丝氨酸暴露的非显著增加，但 NET 形成显著减弱。我们的研究结果表明，中性粒细胞能够调节从健康人血浆中摄取抗坏血酸，以维持细胞内的最佳水平以进行正常功能。然而，更高的口服摄入量可能有助于减少与 NET 形成相关的组织损伤和炎症病理。
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