The effect of zinc on bacterial phagocytosis, killing and cytoprotection in human polymorphonuclear leucocytes

Abstract

Sunzel, B., Holm, S., Reuterving C.-O., Soderberg, T., Hallmans, G . & Hanstrom, L. The effect of zinc on bacterial phagocytosis, killing and cytoprotection in human polymorphonuclear leucocytes.An in vitro study examining the effects of zinc treatment on human PMN cell phagocytosis and killing of Staphylococcus aureus and Staphylococcus epidermidis and the cytoprotection of zinc against staphylococcal toxins. Phagocytosis was studied by transmission electron microscopy using different microbiological techniques, one of which was designed to follow the kinetics of bacterial killing. No effect was found on phagocytosis and bacterial killing. The cytotoxic effects of a crude toxin and an a-toxin extracted from Staphylococcus aureus preparations were studied on human PMN cells using the standard 5'Cr release assay. Both toxins induced a dose-dependent leakage of 51Cr, indicating cell membrane damage. These results were confirmed by electron microscopy during the phagocytosis of S. uureus, where severe PMN cellular degeneration was observed. The addition of zinc to PMN cells strongly inhibited the release of S'Cr. In conclusion, our results show that zinc in higher than physiological concentrations does not inhibit PMN cell functions such as phagocytosis and intracellular killing of S. aureus and S. epidermidis. The addition of zinc may be beneficial in certain clinical situations, such as wound healing, zinc deficiency and infections involving toxin-producing bacteria, e.g. S. aureus.

Zinc Supplementation Modulates NETs Release and Neutrophils’ Degranulation

“…In our experiment, we did not observe any effect of zinc deficiency or zinc supplementation on this process. Our results are in line with Sunzel et al, who also did not report any effect of zinc on phagocytosis [44]. Given that in each of the studies, different species, zinc concentrations and methodology were applied, we suggest that discrepancies between reports can be attributed to differences in experimental setups.…”

“…Sunzel et al observed that granulocytes pretreated with high concentrations of zinc were protected against damage caused by exposure to Staphylococcus aureus and suggested that this effect was due to the neutralization of bacteria-derived toxins [44]. In our study, we observed that zinc limited the number of E. coli in the presence of neutrophils.…”

Impact of the regulatory loci agr, sarA and sae of Staphylococcus aureus on the induction of α‐toxin during device‐related infection resolved by direct quantitative transcript analysis

“…This contradicts the general view that exotoxins are produced preferentially in the later stages of infection. However, one may also assume that α‐toxin plays a role in the evasion of host defences early in infection, as α‐toxin is known to damage macrophages (Bhakdi and Tranum Jensen, 1991) and PMNs (Sunzel et al ., 1995). The downregulation of hla later in the infection may be reasonable for the bacteria, as α‐toxin might possibly be inactivated as a result of the production of specific antibodies and/or host proteases.…”

Elements and COVID-19: A Comprehensive Overview of Studies on Their Blood/Urinary Levels and Supplementation with an Update on Clinical Trials

“…Zn has been reported to (a) increase CD4+ and CD8+ production [ 137 ], (b) enhance NK cell cytotoxicity according to [ 138 ], (c) elevate neutrophil responses to microbes [ 139 ], (d) induce CD4+CD25+Foxp3+ antigen (Ag)-specific regulatory T (Treg) cells [ 134 ], (e) suppress interferon gamma (IFN-γ) production [ 134 ], (f) reduce the number of activated Th cells according to [ 75 ], (g) restore the activity of the Zn-dependent hormone thymulin (FTS) according to [ 75 ] involved in maturation and differentiation of T lymphocytes [ 140 ], (h) decrease infection incidence (INF-I) [ 125 ], modulate interleukin 6 (IL-6) levels [ 141 ], and (i) inhibit the induction of tumor necrosis factor alpha (TNFα) and interleukin 1 beta (IL-1β) mRNA by inhibiting the activity of NF-κB [ 126 ], which is the main regulator of proinflammatory responses [ 125 ]. Moreover, studies on HUT-78 cells conducted by Prasad et al [ 118 ] demonstrated that Zn enhances the production and gene expression of IL-2 and interleukin-2 receptor alpha (IL-2Rα) via NF-kB activation.…”