{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T13:50:29Z","timestamp":1771336229769,"version":"3.50.1"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"japan society for the promotion of science","doi-asserted-by":"publisher","award":["JP16K09972"],"award-info":[{"award-number":["JP16K09972"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Inflammation"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>\n                        <jats:italic>Abstract<\/jats:italic>\n                     <\/jats:title><jats:p>Chronic granulomatous disease (CGD) is a primary immunodeficiency wherein phagocytes are unable to produce reactive oxygen species (ROS) owing to a defect in the nicotinamide adenine dinucleotide phosphate oxidase (NADPH) complex. Patients with CGD experience bacterial and fungal infections and excessive inflammatory disorders. Bone marrow transplantation and gene therapy are theoretically curative; however, residual pathogenic components cause inflammation and\/or organic damage in patients. Moreover, antibiotic treatments may not help in preventing excessive inflammation due to the residual presence of fungal cell wall \u03b2-glucan. Thus, better treatment strategies against CGD are urgently required. Polyethylene glycol\u2013conjugated recombinant porcine <jats:sc>d<\/jats:sc>-amino acid oxidase (PEG-pDAO) supplies ROS to defective NADPH oxidase in neutrophils of patients with CGD, following which the neutrophils regain bactericidal activity <jats:italic>in vitro<\/jats:italic>. In this study, we employed an <jats:italic>in vivo<\/jats:italic> nonviable <jats:italic>Candida albicans<\/jats:italic> (nCA)\u2013induced lung inflammation model of gp91-phox knockout CGD mice and supplied novel PEG conjugates of <jats:italic>Fusarium<\/jats:italic> spp. <jats:sc>d<\/jats:sc>-amino acid oxidase (PEG-fDAO), as it exhibits higher enzyme activity than PEG-pDAO. The body weight, lung weight, and lung pathology were evaluated using three experimental strategies with the <jats:italic>in vivo<\/jats:italic> lung inflammation model to test the efficacy of the ROS-generating enzyme replacement therapy with PEG-fDAO. The lung weight and pathological findings suggest the condition was ameliorated by administration PEG-fDAO, followed by intraperitoneal injection of <jats:sc>d<\/jats:sc>-phenylalanine or <jats:sc>d<\/jats:sc>-proline. Although a more precise protocol is essential, these data reveal the targeted delivery of PEG-fDAO to the nCA-induced inflammation site and show that PEG-fDAO can be used to treat inflammation in CGD <jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1007\/s10753-022-01650-z","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T22:02:23Z","timestamp":1645740143000},"page":"1668-1679","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Treatment with Polyethylene Glycol\u2013Conjugated Fungal d-Amino Acid Oxidase Reduces Lung Inflammation in a Mouse Model of Chronic Granulomatous Disease"],"prefix":"10.1007","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3067-0809","authenticated-orcid":false,"given":"Hiroyuki","family":"Nunoi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiyu","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideaki","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuaki","family":"Aratani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toyoki","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Kataoka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Matsukura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,2,24]]},"reference":[{"key":"1650_CR1","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.hoc.2012.11.002","volume":"27","author":"Steven Holland","year":"2013","unstructured":"Holland, Steven. 2013. Chronic granulomatous disease. Hematology\/Oncology Clinics of North America 27: 89\u201399. https:\/\/doi.org\/10.1016\/j.hoc.2012.11.002.","journal-title":"Hematology\/Oncology Clinics of North America"},{"key":"1650_CR2","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/ni.1703","volume":"10","author":"Luigi Franchi","year":"2009","unstructured":"Franchi, Luigi, Tatjana Eigenbrod, Ra\u00fal. Mu\u00f1oz-Planillo, and Gabriel Nu\u00f1ez. 2009. The inflammasome: A caspase-1 activation platform regulating immune responses and disease pathogenesis. Nature Immunology 10: 241\u2013247. https:\/\/doi.org\/10.1038\/ni.1703.","journal-title":"Nature Immunology"},{"key":"1650_CR3","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1182\/blood-2010-01-264218","volume":"116","author":"Luigi Meissner","year":"2010","unstructured":"Meissner, Luigi, Reinhard A. Seger, Despina Moshous, Alain Fischer, Janine Reichenbach, and Arturo Zychlinsky. 2010. Inflammasome activation in NADPH oxidase defective mononuclear phagocytes from patients with chronic granulomatous disease. Blood 116: 1570\u20131573. https:\/\/doi.org\/10.1182\/blood-2010-01-264218.","journal-title":"Blood"},{"key":"1650_CR4","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1016\/j.freeradbiomed.2009.07.023","volume":"47","author":"David Brown","year":"2009","unstructured":"Brown, David, and Kathy K. Griendling. 2009. Nox proteins in signal transduction. Free Radical Biology & Medicine 47: 1239\u20131253. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2009.07.023.","journal-title":"Free Radical Biology & Medicine"},{"key":"1650_CR5","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/j.bbagen.2014.11.021","volume":"1850","author":"Stjepana Kovac","year":"2015","unstructured":"Kovac, Stjepana, Plamena R. Angelova, Kira M. Holmstr\u00f6m, Ying Zhang, Albena T. Dinkova-Kostova, and Andrey Y. Abramov. 2015. Nrf2 regulates ROS production by mitochondria and NADPH oxidase. Biochimica et Biophysica Acta 1850: 794\u2013801. https:\/\/doi.org\/10.1016\/j.bbagen.2014.11.021.","journal-title":"Biochimica et Biophysica Acta"},{"key":"1650_CR6","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/j.jaci.2014.10.034","volume":"135","author":"Ruby Fernandez-Boyanapalli","year":"2015","unstructured":"Fernandez-Boyanapalli, Ruby, Courtney Frasch, Stacey M. Thomas, Kenneth C. Malcolm, Michael Nicks, Ronald J. Harbeck, Claudia V. Jakubzick, Raphael Nemenoff, Peter M. Henson, Steven M. Holland, and Donna L. Bratton. 2015. Pioglitazone restores phagocyte mitochondrial oxidants and bactericidal capacity in chronic granulomatous disease. Journal of Allergy and Clinical Immunology 135: 517\u2013527. https:\/\/doi.org\/10.1016\/j.jaci.2014.10.034.","journal-title":"Journal of Allergy and Clinical Immunology"},{"key":"1650_CR7","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1038\/s41591-019-0735-5","volume":"26","author":"Kohn, Donald, Claire Booth, Elizabeth M. Kang, Sung-Yun Pai, Kit L. Shaw, Giorgia Santilli, Myriam Armant, Karen F. Buckland, Uimook Choi, Suk See De Ravin, Morna J. Dorsey, Caroline Y. Kuo, Diego Leon-Rico, Christine Rivat, Natalia Izotova, Kimberly Gilmour, Katie Snell, Jinhua Xu-Bayford Dip, Jinan Darwish, Emma C Morris, Dayna Terrazas, Leo D. Wang, Christopher A. Bauser, Tobias Paprotka, Douglas B. Kuhns, John Gregg, Hayley E. Raymond, John K. Everett, Geraldine Honnet, Luca Biasco, Peter E. Newburger, Frederic D. Bushman, Manuel Grez, Bobby H. Gaspar, David A. Williams, Harry L. Malech, Anne Galy, Adrian J. 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The Journal of Pathology 214: 434\u2013444. https:\/\/doi.org\/10.1002\/path.2298.","journal-title":"The Journal of Pathology"},{"key":"1650_CR18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009631","volume":"5","author":"Segal Brahm","year":"2010","unstructured":"Brahm, Segal, Wei Han, Jennifer J. Bushey, Myungsoo Joo, Zahida Bhatti, Joy Feminella, Carly G. Dennis, Robert R. Vethanayagam, Fiona E. Yull, Maegan Capitano, Paul K. Wallace, Hans Minderman, John W. Christman, Michael B. Sporn, Jefferson Chan, Donald C. Vin, Steven M. Holland, Luigina R. Romani, Sarah L. Gaffen, Michael L. Freeman, and Timothy S. Blackwell. 2010. NADPH oxidase limits innate immune responses in the lungs in mice. 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The American Journal of Pathology 149: 2005\u20132022. https:\/\/doi.org\/10.1164\/ajrccm.156.1.9609140.","journal-title":"The American Journal of Pathology"}],"container-title":["Inflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10753-022-01650-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10753-022-01650-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10753-022-01650-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T00:06:59Z","timestamp":1655251619000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10753-022-01650-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,24]]},"references-count":21,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["1650"],"URL":"https:\/\/doi.org\/10.1007\/s10753-022-01650-z","relation":{},"ISSN":["0360-3997","1573-2576"],"issn-type":[{"value":"0360-3997","type":"print"},{"value":"1573-2576","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,24]]},"assertion":[{"value":"12 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 February 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"DECLARATIONS"}},{"value":"This study was approved by the Ethics Review Board of the Faculty of Pharmaceutical Sciences (Permission number: 2017-P-027). This study was performed in line with the guidelines of the Laboratory Protocol of Animal Handling, Sojo University Faculty of Pharmaceutical Sciences. All animals were housed under specific pathogen-free conditions.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"All authors have approved the manuscript and agree with submission.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}