Abstract
Zinc plays an important physiological role in the entire body, especially in the immune system. It is one of the most abundant microelements in our organism and an essential component of enzymes and antibacterial proteins. Zinc levels were reported to be correlated with the intensity of innate immunity responses, especially those triggered by neutrophils. However, as the results are fragmentary, the phenomenon is still not fully understood and requires further research. In this study, we aimed to perform a comprehensive assessment and study the impact of zinc on several basic neutrophils’ functions in various experimental setups. Human and murine neutrophils were preincubated in vitro with zinc, and then phagocytosis, oxidative burst, degranulation and release of neutrophil extracellular traps (NETs) were analyzed. Moreover, a murine model of zinc deficiency and zinc supplementation was introduced in the study and the functions of isolated cells were thoroughly studied. We showed that zinc inhibits NETs release as well as degranulation in both human and murine neutrophils. Our study revealed that zinc decreases NETs release by inhibiting citrullination of histone H3. On the other hand, studies performed in zinc-deficient mice demonstrated that low zinc levels result in increased release of NETs and enhanced neutrophils degranulation. Overall, it was shown that zinc affects neutrophils’ functions in vivo and in vitro. Proper zinc level is necessary to maintain efficient functioning of the innate immune response.
Highlights
Zinc is the second most abundant intracellular metal in the human body
Pretreatment of cells with zinc showed strong inhibition of neutrophil extracellular traps (NETs) release after stimulation with phorbol 1212-myristate 13-acetate (PMA), calcium ionophore A23187 (CI), and LPS isolated from P. aeruginosa (Figure 1a–c,h)
We investigated the impact of zinc on the functions of neutrophils isolated from healthy humans and mice
Summary
Zinc is the second most abundant intracellular metal in the human body. Half of the zinc is located in the cytoplasm, whereas 30–40% in the nucleus, and about 10% in the cell membrane [1]. Zinc deficiency often affects pregnant women, children, the elderly, vegetarians, and patients suffering from intestinal diseases [2]. Diminished zinc concentration was observed in patients suffering from diabetes mellitus type 2 and in patients with chronic kidney disease. Lowered zinc levels have been correlated with an increased risk of breast cancer [3]. Zinc deficiency impairs macrophages’ and neutrophils’ ability to phagocyte and inhibits chemotaxis, NK cell activity and production of reactive oxygen species [2,4,5,6,7]
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