Institute of Basic Medical Sciences, Meizhou People's Hospital, Meizhou, China.
Guangdong Engineering Technological Research Center for Clinical Molecular Diagnosis and Antibody Drugs, Meizhou, China.
Front Immunol. 2024 Sep 2;15:1436747. doi: 10.3389/fimmu.2024.1436747. eCollection 2024.
Natural killer (NK) cells are proposed to participate in coronary artery disease (CAD) development. However, little is known about how CAD patients' NK cells respond to different stimulatory factors in terms of proliferation capability.
Twenty-nine CAD patients' peripheral blood NK cells were isolated and individually treated with IL-2, IL-12, IL-15, IL-18, IL-21, cortisone acetate, hydrocortisone, or ascorbic acid for 36 hours, followed by cell cycle analysis using flow cytometry. The ratio of S and G2/M phase cell number to total cell number was defined as a proliferation index (PrI) and used for proliferative capability indication. The results showed that these eight factors resulted in different life cycle changes in the 29 NK cell samples. Remarkably, 28 out of 29 NK cell samples showed an obvious increase in PrI upon ascorbic acid treatment. The serum lactate dehydrogenase (LDH) level of the 29 CAD patients was measured. The results showed a negative correlation between serum LDH level and the CAD patients' NK cell PrI upon stimulation of interleukins, but not the non-interleukin stimulators. Consistently, a retrospective analysis of 46 CAD patients and 32 healthy donors showed that the circulating NK cell number negatively correlated with the serum LDH level in CAD patients. Unexpectedly, addition of LDH to NK cells significantly enhanced the production of IFN-γ, IL-10 and TNF-α, suggesting a strong regulatory role on NK cell's function.
Ascorbic acid could promote the proliferation of the CAD patients' NK cells; LDH serum level may function as an indicator for NK cell proliferation capability and an immune-regulatory factor.
自然杀伤 (NK) 细胞被认为参与了冠状动脉疾病 (CAD) 的发展。然而，对于 CAD 患者的 NK 细胞在增殖能力方面对不同刺激因素的反应，我们知之甚少。
分离 29 例 CAD 患者外周血 NK 细胞，分别用 IL-2、IL-12、IL-15、IL-18、IL-21、醋酸考的松、氢化考的松或抗坏血酸处理 36 小时，然后用流式细胞术进行细胞周期分析。S 和 G2/M 期细胞数与总细胞数的比值定义为增殖指数 (PrI)，用于指示增殖能力。结果表明，这 8 种因素导致 29 个 NK 细胞样本的细胞周期发生不同的变化。值得注意的是，29 个 NK 细胞样本中有 28 个在抗坏血酸处理后 PrI 明显增加。测量了 29 例 CAD 患者的血清乳酸脱氢酶 (LDH) 水平。结果表明，血清 LDH 水平与 CAD 患者 NK 细胞在受到白细胞介素刺激后的 PrI 呈负相关，但与非白细胞介素刺激物无关。同样，对 46 例 CAD 患者和 32 名健康供体的回顾性分析表明，循环 NK 细胞数量与 CAD 患者血清 LDH 水平呈负相关。出乎意料的是，向 NK 细胞中添加 LDH 可显著增强 IFN-γ、IL-10 和 TNF-α的产生，表明其对 NK 细胞功能具有很强的调节作用。
抗坏血酸可促进 CAD 患者 NK 细胞的增殖；血清 LDH 水平可能是 NK 细胞增殖能力的指标和免疫调节因子。
