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 alpha-toxin extracted from Staphylococcus aureus preparations were studied on human PMN cells using the standard 51Cr 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. aureus, where severe PMN cellular degeneration was observed. The addition of zinc to PMN cells strongly inhibited the release of 51Cr. 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.
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Front Physiol
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Walther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany.
Two-pore channels (TPCs) are adenine nucleotide and phosphoinositide regulated cation channels. NAADP activates and ATP blocks TPCs, while the endolysosomal phosphoinositide PI(3,5)P activates TPCs. TPCs are ubiquitously expressed including expression in the innate as well as the adaptive immune system.
View Article and Find Full Text PDFActa Biochim Biophys Sin (Shanghai)
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International Cancer Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, Shenzhen University Medical School, Shenzhen 518060, China.
Relieving hypoxia in the tumor microenvironment (TME) promotes innate and adaptive immunity. Our previous research demonstrated that reoxygenation of the TME promotes the phagocytosis and tumor-killing functions of tumor-associated macrophages (TAMs) by upregulating pyruvate carboxylase (PCB). However, the mechanism remains obscure.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Molecular Genetics and Infection Biology, University of Greifswald, 17489, Greifswald, Germany.
In recent years, increased numbers of severe Streptococcus dysgalactiae subsp. equisimilis (SDSE) infections, including necrotizing soft tissue infections (NSTIs), have been reported. One of the main virulence factors of SDSE is streptokinase (Ska).
View Article and Find Full Text PDFNat Commun
January 2025
School of Pharmacy, Key Laboratory of Smart Drug Delivery Ministry of Education, State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, 201203, China.
Adoptive transfer of genetically or nanoparticle-engineered macrophages represents a promising cell therapy modality for treatment of solid tumor. However, the therapeutic efficacy is suboptimal without achieving a complete tumor regression, and the underlying mechanism remains elusive. Here, we discover a subpopulation of cancer cells with upregulated CD133 and programmed death-ligand 1 in mouse melanoma, resistant to the phagocytosis by the transferred macrophages.
View Article and Find Full Text PDFPLoS Pathog
January 2025
School of Clinical Dentistry, University of Sheffield, Sheffield, United Kingdom.
Porphyromonas gingivalis (Pg) is a keystone pathogen in periodontitis, a highly prevalent disease manifested by chronic inflammation of the periodontium, alveolar bone resorption and tooth loss. During periodontitis pathobionts such as Pg can enter the bloodstream and growing evidence correlates periodontitis with increased risk of cardiovascular and neurodegenerative diseases. However, the mechanism by which immune cells respond to Pg challenge in vivo remains elusive.
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