{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T08:49:17Z","timestamp":1791449357360,"version":"4.3.3"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":53,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100011787","name":"Heilongjiang Provincial Science and Technology Department","doi-asserted-by":"publisher","award":["2022ZXJ03C01"],"award-info":[{"award-number":["2022ZXJ03C01"]}],"id":[{"id":"10.13039\/501100011787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["LH2023H019"],"award-info":[{"award-number":["LH2023H019"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Aluminum\u2010associated interstitial lung disease is an exposure\u2010related fibrotic lung disorder, but the metabolic and innate immune mechanisms underlying persistent pulmonary remodeling after aluminum exposure remain incompletely understood. We investigated whether lactate\u2010associated neutrophil dysfunction contributes to lung injury and fibrosis\u2010like remodeling following AlCl\n                    <jats:sub>3<\/jats:sub>\n                    aerosol exposure. Rats were subjected to repeated AlCl\n                    <jats:sub>3<\/jats:sub>\n                    aerosol exposure with or without pharmacological inhibition of lactate transport using the monocarboxylate transporter 1 inhibitor AZD3965. Pulmonary injury, lactate accumulation, inflammatory responses, oxidative stress, DNA damage response signaling, and fibrosis\u2010like remodeling were assessed. Bone marrow\u2010derived rat neutrophils were treated with sodium L\u2010lactate in the presence or absence of AZD3965 to evaluate chemotaxis, oxidative burst, mitochondrial membrane potential, calcium signaling, intracellular lactate accumulation, and neutrophil extracellular trap (NET)\u2010associated responses. In addition, a supportive human cohort comprising patients with aluminum exposure\u2010related interstitial lung disease (Al\u2010ILD), patients with nonaluminum interstitial lung disease (non\u2010Al\u2010ILD), and healthy controls was analyzed using quantitative chest computed tomography (CT), pulmonary function testing, and peripheral blood transcriptomics. Repeated AlCl\n                    <jats:sub>3<\/jats:sub>\n                    aerosol exposure was associated with pulmonary aluminum deposition, lactate accumulation, inflammatory injury, oxidative stress, DNA damage response signaling, neutrophil abnormalities, and collagen\u2010rich fibrosis\u2010like remodeling in rats. In\u00a0vitro, high\u2010lactate\u2010associated metabolic stress impaired neutrophil chemotaxis, oxidative burst, mitochondrial membrane potential, calcium signaling, and NET\u2010associated responses. AZD3965 reduced intracellular and pulmonary lactate accumulation and partially ameliorated neutrophil dysfunction, inflammatory injury, oxidative stress, and fibrosis\u2010like remodeling in experimental models. In the supportive human cohort, patients with Al\u2010ILD showed greater quantitative CT\u2010defined parenchymal abnormality burden and lower forced vital capacity and diffusing capacity for carbon monoxide than patients with non\u2010Al\u2010ILD. Peripheral blood transcriptomic analysis revealed enrichment of innate immune, cytokine signaling, extracellular matrix organization, and NET\u2010related pathways in Al\u2010ILD. Collectively, these findings indicate that AlCl\n                    <jats:sub>3<\/jats:sub>\n                    aerosol exposure is associated with pulmonary lactate accumulation, neutrophil dysfunction, and fibrosis\u2010like remodeling. Pharmacological modulation of lactate transport provides supportive evidence for the involvement of lactate\u2010associated metabolic regulation in this process, although further studies are required to define the specific molecular targets involved. The integration of experimental and supportive human findings suggests that the lactate\u2013neutrophil dysfunction axis may represent a mechanistically relevant feature of aluminum\u2010associated lung injury and remodeling.\n                  <\/jats:p>","DOI":"10.1002\/biof.70146","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T03:30:37Z","timestamp":1787542237000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>AlCl<\/scp>\n                    <sub>3<\/sub>\n                    Aerosol Exposure Is Associated With Pulmonary Lactate Accumulation, Neutrophil Dysfunction, and Fibrosis\u2010Like Remodeling"],"prefix":"10.1002","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4956-1149","authenticated-orcid":false,"given":"Jiayu","family":"Qin","sequence":"first","affiliation":[{"name":"Respiratory and Critical Care Medicine Department The Fourth Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fushi","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengjie","family":"Ye","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangxin","family":"Yao","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xintong","family":"Wang","sequence":"additional","affiliation":[{"name":"Respiratory and Critical Care Medicine Department The Fourth Affiliated Hospital of Harbin Medical University  Harbin 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University  Daqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7494-2354","authenticated-orcid":false,"given":"Chunli","family":"Che","sequence":"additional","affiliation":[{"name":"Respiratory and Critical Care Medicine Department The Fourth Affiliated Hospital of Harbin Medical University  Harbin 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