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Here, we show that BWPs induce slight cellular superoxide (\u2022O2\u2013) at low doses (&amp;lt;10 \u03bcg mL\u20131) but suppress it dose-dependently at higher doses. In contrast, highway PM2.5 neither significantly induces nor suppresses cellular \u2022O2\u2013 generation. Using Fe alone or mixed with isoprene secondary organic aerosols or 9,10-phenanthrenequinone, typical organic compounds known to induce cellular \u2022O2\u2013 via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, we demonstrate that both Fe2+ and Fe3+ actively suppress baseline and organic-induced \u2022O2\u2013 in a dose-dependent manner. Through inhibition experiments and qRT-PCR analysis, we suggest the following mechanisms for Fe suppression on cellular \u2022O2\u2013: exogenous Fe replenishes the intracellular labile iron pool or complexes with organics. This alleviates organic-induced iron deficiency, reduces NADPH oxidase activity, thereby reducing \u2022O2\u2013 release. Fe simultaneously consumes \u2022O2\u2013 via direct chemical reactions. This work reveals iron as a suppressor rather than a promoter of organic-induced \u2022O2\u2013 generation in macrophages, operating through restoration of iron homeostasis and direct chemical quenching. These findings underscore the importance of considering both metal and organic constituents in assessing the health impacts of complex environmental mixtures.<\/jats:p>","DOI":"10.1021\/acs.est.6c06554","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T16:01:54Z","timestamp":1788796914000},"page":"26158-26167","source":"Crossref","is-referenced-by-count":1,"title":["A\nBrake on Toxicity:\nIron Suppresses Organic-Induced\nSuperoxide Generation in Macrophages"],"prefix":"10.1021","volume":"60","author":[{"given":"Yuting","family":"Shen","sequence":"first","affiliation":[{"name":"The Hong Kong University of Science and Technology (Guangzhou) , , ,","place":["Guangzhou, China, 511400"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasey C.","family":"Edwards","sequence":"additional","affiliation":[{"name":"University of California, Irvine , , , ,","place":["Irvine, California, United States, 92697"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6645-7300","authenticated-orcid":true,"given":"Sukriti","family":"Kapur","sequence":"additional","affiliation":[{"name":"University of California, Irvine , , , ,","place":["Irvine, California, United States, 92697"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianle","family":"Pan","sequence":"additional","affiliation":[{"name":"Guangzhou Institute of Geochemistry, Chinese Academy of Sciences , , ,","place":["Guangzhou, China, 510640"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3485-6304","authenticated-orcid":true,"given":"Weiwei","family":"Hu","sequence":"additional","affiliation":[{"name":"Guangzhou Institute of Geochemistry, Chinese Academy of Sciences , , ,","place":["Guangzhou, China, 510640"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9857-4608","authenticated-orcid":true,"given":"Shengzhen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Sun Yat-Sen University , , ,","place":["Zhuhai, China, 519082"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Shiraiwa","sequence":"additional","affiliation":[{"name":"University of California, Irvine , , , ,","place":["Irvine, California, United States, 92697"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4845-2749","authenticated-orcid":true,"given":"Ting","family":"Fang","sequence":"additional","affiliation":[{"name":"The Hong Kong University of Science and Technology (Guangzhou) , , ,","place":["Guangzhou, China, 511400"]},{"name":"The Hong Kong University of Science and Technology (Guangzhou) , , ,","place":["Guangzhou, China, 511400"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"issue":"2","key":"2026092210093872700_cit1","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1093\/ije\/dyaa230","article-title":"Long-term exposure to iron and copper in fine particulate air pollution\nand their combined impact on reactive oxygen species concentration\nin lung fluid: a population-based cohort study of cardiovascular disease\nincidence and mortality in Toronto, Canada.","volume":"50","author":"Zhang","year":"2021","journal-title":"Int. J. Epidemiol."},{"issue":"6","key":"2026092210093872700_cit2","doi-asserted-by":"publisher","first-page":"3807","DOI":"10.1021\/acs.est.0c05931","article-title":"A Population-Based Cohort Study of Respiratory Disease and Long-Term\nExposure to Iron and Copper in Fine Particulate Air Pollution and\nTheir Combined Impact on Reactive Oxygen Species Generation in Human\nLungs","volume":"55","author":"Zhang","year":"2021","journal-title":"Environ. Sci. Technol."},{"issue":"14","key":"2026092210093872700_cit3","doi-asserted-by":"publisher","first-page":"8777","DOI":"10.1021\/acs.est.5b01449","article-title":"Single Exposure\nto near Roadway Particulate Matter Leads to Confined Inflammatory\nand Defense Responses: Possible Role of Metals","volume":"49","author":"Pardo","year":"2015","journal-title":"Environ. Sci. Technol."},{"key":"2026092210093872700_cit4","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.atmosenv.2016.09.005","article-title":"Dose-dependent\nintracellular reactive oxygen and nitrogen species\n(ROS\/RNS) production from particulate matter exposure: comparison\nto oxidative potential and chemical composition","volume":"144","author":"Tuet","year":"2016","journal-title":"Atmos. Environ."},{"issue":"21","key":"2026092210093872700_cit5","doi-asserted-by":"publisher","first-page":"12784","DOI":"10.1021\/acs.est.9b03823","article-title":"Oxidative Potential\nof Particulate Matter and Generation of Reactive Oxygen Species in\nEpithelial Lining Fluid","volume":"53","author":"Fang","year":"2019","journal-title":"Environ. Sci. 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Cell\nBiol."},{"issue":"3","key":"2026092210093872700_cit29","doi-asserted-by":"publisher","DOI":"10.3390\/ph12030120","article-title":"Impairment\nof the developing human brain in iron deficiency: correlations to\nfindings in experimental animals and prospects for early intervention\ntherapy","volume":"12","author":"Markova","year":"2019","journal-title":"Pharmaceuticals"},{"issue":"12","key":"2026092210093872700_cit30","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1016\/j.tem.2024.04.015","article-title":"Why cells\nneed iron: a compendium\nof iron utilisation","volume":"35","author":"Teh","year":"2024","journal-title":"Trends Endocrinol. Metab."},{"issue":"6","key":"2026092210093872700_cit31","doi-asserted-by":"publisher","first-page":"3362","DOI":"10.1097\/MS9.0000000000003100","article-title":"Iron homeostasis\nand health: understanding its role beyond blood health\u2013a narrative\nreview","volume":"87","author":"Obeagu","year":"2025","journal-title":"Annals Med. 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