Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany; Health Campus Immunology, Infection and Inflammation (GC-I3), Medical Faculty, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany; Center of Health and Medical Prevention (CHaMP), Otto-von-Guericke University, Magdeburg, Germany.
J Trace Elem Med Biol. 2023 May;77:127152. doi: 10.1016/j.jtemb.2023.127152. Epub 2023 Mar 11.
Zinc, one of the most important essential trace elements in the human body, regulates a wide range of cellular functions of immune cells, such as proliferation, differentiation and survival. Zinc deficiency affects both the innate and adaptive immune system. Zinc supplementation was discussed as possible therapy for infectious diseases and T cell-mediated autoimmune diseases. However, the influence of commercial zinc preparations on proliferation and cytokine production of resting and antigen-stimulated peripheral blood mononuclear cells (PBMC) has not yet been completely investigated.
Here, we examined whether zinc aspartate (Unizink®), an approved drug to treat zinc deficiency in patients, induces proliferation, cytokine production, and induction of apoptosis/caspase 3/7 activity of resting PBMC under high-density cell culture condition. In addition, we performed antigen-specific proliferation experiments, where PBMCs of healthy donors vaccinated against Influenza A (H1N1) and/or SARS-CoV-2 were stimulated with Influenza A (H1N1) peptides or SARS-CoV-2 peptides as well as the Mixed Lymphocyte Culture (MLC) in the presence of increasing concentrations of zinc aspartate.
We observed a dose-dependent enhancement of proliferation and induction of cytokine production (IFN-γ, IL-5, GM-CSF and CXCL10) of resting PBMC in presence of zinc aspartate. The number of cells with active caspase 3/7 and, consecutively, the amount of cells undergoing apoptosis steadily decreased in presence of zinc aspartate. Moreover, zinc aspartate was capable of stimulating antigen-specific PBMC proliferation using MLC or influenza A (H1N1) and SARS-CoV-2 peptides in both a dose-dependent and a donor-specific manner. In the absence of zinc aspartate, we clearly could discriminate two groups of responders: low and high responders to antigenic stimulation. The addition of increasing concentration of zinc aspartate significantly stimulated the proliferation of PBMC from low responders, but not from high responders.
Taken together, our results suggest that zinc aspartate induces the proliferation of resting and antigen-stimulated PBMCs under high-density cell culture conditions. Thus, zinc might represent a supportive treatment in patients suffering from infectious diseases.
锌是人体内最重要的必需微量元素之一，它调节免疫细胞的多种细胞功能，如增殖、分化和存活。缺锌会影响先天免疫和适应性免疫系统。锌补充剂被讨论为治疗传染病和 T 细胞介导的自身免疫性疾病的可能疗法。然而，商业锌制剂对静息和抗原刺激的外周血单个核细胞 (PBMC) 的增殖和细胞因子产生的影响尚未完全研究。
在这里，我们研究了锌天冬氨酸（Unizink®）是否在高密度细胞培养条件下诱导静息 PBMC 的增殖、细胞因子产生和诱导凋亡/半胱天冬酶 3/7 活性。此外，我们进行了抗原特异性增殖实验，其中健康供体的 PBMC 接种了流感 A (H1N1) 和/或 SARS-CoV-2 疫苗，并用流感 A (H1N1) 肽或 SARS-CoV-2 肽以及混合淋巴细胞培养 (MLC) 刺激，同时存在锌天冬氨酸的浓度逐渐增加。
我们观察到在锌天冬氨酸存在下，静息 PBMC 的增殖和细胞因子产生（IFN-γ、IL-5、GM-CSF 和 CXCL10）呈剂量依赖性增强。锌天冬氨酸存在时，具有活性半胱天冬酶 3/7 的细胞数量和随之发生凋亡的细胞数量稳步减少。此外，锌天冬氨酸能够以剂量依赖性和供体特异性的方式刺激使用 MLC 或流感 A (H1N1) 和 SARS-CoV-2 肽的抗原特异性 PBMC 增殖。在没有锌天冬氨酸的情况下，我们可以清楚地区分两组对抗原刺激的反应者：低反应者和高反应者。增加锌天冬氨酸浓度可显著刺激低反应者的 PBMC 增殖，但不能刺激高反应者的 PBMC 增殖。
综上所述，我们的结果表明，锌天冬氨酸在高密度细胞培养条件下诱导静息和抗原刺激的 PBMC 增殖。因此，锌可能代表感染性疾病患者的支持性治疗。
