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Iron is considered to be an invaluable constituent of host immune defense and plays a dual role in immunity. It is a well\u2010known component of antimicrobial proteins and is a necessary microelement for pathogen survival. The aim of this study was to broaden the knowledge regarding the impact of iron on the function of neutrophils. Neutrophils from healthy blood donors and patients with mild iron\u2010deficiency anemia and HL\u201060 cells differentiated toward granulocyte\u2010like cells were incubated with Fe<jats:sup>2+<\/jats:sup>, Fe<jats:sup>3+<\/jats:sup> or holo\u2010transferrin (holo\u2010Tf). Moreover, we isolated murine neutrophils of <jats:italic>HFE<\/jats:italic> gene knockout (KO) mice and mice fed iron\u2010deficient, iron\u2010equivalent and high\u2010iron diets. We analyzed the release of NETs, phagocytosis, degranulation of azurophilic granules, ROS release, bactericidal activity of granulocytes against <jats:italic>Escherichia coli<\/jats:italic> and neutrophil elastase (NE) activity. We show that holo\u2010Tf inhibits the release of NETs stimulated by phorbol 12\u2010myristate 13\u2010acetate by inhibiting NE activity. Studies performed in mice models reveal that iron overload inhibits the release of NETs and ROS production in neutrophils isolated from <jats:italic>HFE<\/jats:italic> KO mice and mice fed a high\u2010iron diet. No impact of a low\u2010iron diet on neutrophil phagocytosis, ROS production or release of NETs was observed. Our study underscores the physiological significance of iron in neutrophil function, specifically in the release of NETs.<\/jats:p>","DOI":"10.1111\/imcb.12509","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T16:53:37Z","timestamp":1635526417000},"page":"87-100","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Iron excess affects release of neutrophil extracellular traps and reactive oxygen species but does not influence other functions of neutrophils"],"prefix":"10.1111","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3036-9864","authenticated-orcid":false,"given":"Weronika","family":"Ku\u017amicka","sequence":"first","affiliation":[{"name":"Postgraduate School of Molecular Medicine Medical University of Warsaw Warsaw Poland"},{"name":"Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age Medical University of Warsaw Warsaw 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