{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:40:21Z","timestamp":1790361621942,"version":"4.1.0"},"reference-count":275,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:00:00Z","timestamp":1715904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council","award":["MR\/X001504\/1"],"award-info":[{"award-number":["MR\/X001504\/1"]}]},{"name":"Medical Research Council","award":["MR\/T016760\/1"],"award-info":[{"award-number":["MR\/T016760\/1"]}]},{"name":"Medical Research Council","award":["MR\/P022847\/1"],"award-info":[{"award-number":["MR\/P022847\/1"]}]},{"name":"Department for the Economy Northern Ireland","award":["MR\/X001504\/1"],"award-info":[{"award-number":["MR\/X001504\/1"]}]},{"name":"Department for the Economy Northern Ireland","award":["MR\/T016760\/1"],"award-info":[{"award-number":["MR\/T016760\/1"]}]},{"name":"Department for the Economy Northern Ireland","award":["MR\/P022847\/1"],"award-info":[{"award-number":["MR\/P022847\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neutrophil-derived proteases are critical to the pathology of many inflammatory lung diseases, both chronic and acute. These abundant enzymes play roles in key neutrophil functions, such as neutrophil extracellular trap formation and reactive oxygen species release. They may also be released, inducing tissue damage and loss of tissue function. Historically, the neutrophil serine proteases (NSPs) have been the main subject of neutrophil protease research. Despite highly promising cell-based and animal model work, clinical trials involving the inhibition of NSPs have shown mixed results in lung disease patients. As such, the cutting edge of neutrophil-derived protease research has shifted to proteases that have had little-to-no research in neutrophils to date. These include the cysteine and serine cathepsins, the metzincins and the calpains, among others. This review aims to outline the previous work carried out on NSPs, including the shortcomings of some of the inhibitor-orientated clinical trials. Our growing understanding of other proteases involved in neutrophil function and neutrophilic lung inflammation will then be discussed. Additionally, the potential of targeting these more obscure neutrophil proteases will be highlighted, as they may represent new targets for inhibitor-based treatments of neutrophil-mediated lung inflammation.<\/jats:p>","DOI":"10.3390\/ijms25105492","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T12:02:23Z","timestamp":1715947343000},"page":"5492","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Neutrophil-Derived Proteases in Lung Inflammation: Old Players and New Prospects"],"prefix":"10.3390","volume":"25","author":[{"given":"Coby J.","family":"Cheetham","sequence":"first","affiliation":[{"name":"Airway Innate Immunity Research (AiiR) Group, Wellcome-Wolfson Institute for Experimental Medicine and Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen\u2019s University Belfast, Belfast BT9 7BL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6492-7310","authenticated-orcid":false,"given":"Michael C.","family":"McKelvey","sequence":"additional","affiliation":[{"name":"Airway Innate Immunity Research (AiiR) Group, Wellcome-Wolfson Institute for Experimental Medicine and Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen\u2019s University Belfast, Belfast BT9 7BL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel F.","family":"McAuley","sequence":"additional","affiliation":[{"name":"Wellcome-Wolfson Institute for Experimental Medicine, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford C.","family":"Taggart","sequence":"additional","affiliation":[{"name":"Airway Innate Immunity Research (AiiR) Group, Wellcome-Wolfson Institute for Experimental Medicine and Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen\u2019s University Belfast, Belfast BT9 7BL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S2213-2600(21)00511-7","article-title":"Global, Regional, and National Prevalence of, and Risk Factors for, Chronic Obstructive Pulmonary Disease (COPD) in 2019: A Systematic Review and Modelling Analysis","volume":"10","author":"Adeloye","year":"2022","journal-title":"Lancet Respir. 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