Carr Anitra C, Bozonet Stephanie, Pullar Juliet, Spencer Emma, Rosengrave Patrice, Shaw Geoff
Department of Pathology and Biomedical Science, University of Otago, Christchurch 8140, New Zealand.
Centre for Postgraduate Nursing Studies, University of Otago, Christchurch 8140, New Zealand.
Antioxidants (Basel). 2021 Oct 13;10(10):1607. doi: 10.3390/antiox10101607.
Vitamin C (ascorbate) plays an important role in neutrophil function and is accumulated by the cells either directly via vitamin C transporters (SVCT) or indirectly following oxidation to dehydroascorbic acid. Septic patients are known to have significantly depleted plasma ascorbate status, but little is known about the ascorbate content of their circulating cells. Therefore, we assessed the ascorbate concentrations of plasma, leukocytes and erythrocytes from septic patients and compared these to healthy controls. Non-fasting blood samples were collected from healthy volunteers ( = 20) and critically ill patients with sepsis ( = 18). The ascorbate content of the plasma and isolated neutrophils and erythrocytes was measured using HPLC and plasma myeloperoxidase concentrations were determined using ELISA. Ex vivo uptake of ascorbate and dehydroascorbic acid by neutrophils from septic patients was also assessed. Neutrophils isolated from septic patients had comparable intracellular ascorbate content to healthy volunteers (0.33 vs. 0.35 nmol/10 cells, > 0.05), despite significantly lower plasma concentrations than the healthy controls (14 vs. 88 µmol/L, < 0.001). In contrast, erythrocytes from septic patients had significantly lower intracellular ascorbate content than healthy controls (30 vs. 69 µmol/L, = 0.002), although this was 2.2-fold higher than the matched plasma concentrations in the patients ( = 0.008). Higher concentrations of myeloperoxidase, a source of reactive oxygen species, were observed in the septic patients relative to healthy controls (194 vs. 14 mg/mL, < 0.0001). In contrast to neutrophils from healthy volunteers, the neutrophils from septic patients demonstrated elevated uptake of extracellular ascorbate. Overall, neutrophils from septic patients exhibited comparable intracellular ascorbate content to those from healthy controls, despite the patients presenting with hypovitaminosis C. The mechanisms involved are currently uncertain, but could include increased generation of dehydroascorbic acid in septic patients, enhanced basal activation of their neutrophils or upregulation of their vitamin C transporters.
维生素C（抗坏血酸）在中性粒细胞功能中起重要作用，细胞可通过维生素C转运体（SVCT）直接摄取维生素C，也可在其氧化为脱氢抗坏血酸后间接摄取。已知脓毒症患者血浆抗坏血酸水平显著降低，但对其循环细胞中的抗坏血酸含量了解甚少。因此，我们评估了脓毒症患者血浆、白细胞和红细胞中的抗坏血酸浓度，并将其与健康对照者进行比较。从健康志愿者（n = 20）和重症脓毒症患者（n = 18）中采集非空腹血样。使用高效液相色谱法测定血浆、分离的中性粒细胞和红细胞中的抗坏血酸含量，使用酶联免疫吸附测定法测定血浆髓过氧化物酶浓度。还评估了脓毒症患者中性粒细胞对体外抗坏血酸和脱氢抗坏血酸的摄取。尽管脓毒症患者的血浆浓度明显低于健康对照者（14 vs. 88 μmol/L，P < 0.001），但从脓毒症患者分离的中性粒细胞的细胞内抗坏血酸含量与健康志愿者相当（0.33 vs. 0.35 nmol/10⁶细胞，P > 0.05）。相比之下，脓毒症患者红细胞的细胞内抗坏血酸含量显著低于健康对照者（30 vs. 69 μmol/L，P = 0.002），尽管这比患者匹配的血浆浓度高2.2倍（P = 0.008）。与健康对照者相比，脓毒症患者中观察到更高浓度的髓过氧化物酶（一种活性氧来源）（194 vs. 14 ng/mL，P < 0.0001）。与健康志愿者的中性粒细胞不同，脓毒症患者的中性粒细胞表现出细胞外抗坏血酸摄取增加。总体而言，尽管脓毒症患者存在维生素C缺乏症，但其中性粒细胞的细胞内抗坏血酸含量与健康对照者相当。目前尚不清楚其中涉及的机制，但可能包括脓毒症患者中脱氢抗坏血酸生成增加、中性粒细胞基础激活增强或其维生素C转运体上调。
Zotero 插件
