{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1362825895254941568.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.4049/jimmunol.170.8.4209"}},{"identifier":{"@type":"URI","@value":"https://academic.oup.com/jimmunol/article-pdf/170/8/4209/62567837/4209.pdf"}},{"identifier":{"@type":"PMID","@value":"12682254"}}],"dc:title":[{"@value":"Hyperoxia Mediates Acute Lung Injury and Increased Lethality in Murine\n                    <i>Legionella</i>\n                    Pneumonia: The Role of Apoptosis"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title>\n                  <jats:p>Legionella pneumophila is a major cause of life-threatening pneumonia, which is characterized by a high incidence of acute lung injury and resultant severe hypoxemia. Mechanical ventilation using high oxygen concentrations is often required in the treatment of patients with L. pneumophila pneumonia. Unfortunately, oxygen itself may propagate various forms of tissue damage, including acute lung injury. The effect of hyperoxia as a cofactor in the course of L. pneumophila pneumonia is poorly understood. In this study, we show that exposure to hyperoxic conditions during the evolution of pneumonia results in a marked increase in lethality in mice with Legionella pneumonia. The enhanced lethality was associated with an increase in lung permeability, but not changes in either lung bacterial burden or leukocyte accumulation. Interestingly, accelerated apoptosis as evidenced by assessment of histone-DNA fragments and caspase-3 activity were noted in the infected lungs of mice exposed to hyperoxia. TUNEL staining of infected lung sections demonstrated increased apoptosis in hyperoxic mice, predominantly in macrophages and alveolar epithelial cells. In vitro exposure of primary murine alveolar epithelial cells to Legionella in conjunction with hyperoxia accelerated apoptosis and loss of barrier function. Fas-deficient mice demonstrated partial resistance to the lethal effects of Legionella infection induced by hyperoxia, which was associated with attenuated apoptosis in the lung. These results demonstrate that hyperoxia serves as an important cofactor for the development of acute lung injury and lethality in L. pneumophila pneumonia. Exaggerated apoptosis, in part through Fas-mediated signaling, may accelerate hyperoxia-induced acute lung injury in Legionella pneumonia.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1382825895254941441","@type":"Researcher","foaf:name":[{"@value":"Kazuhiro Tateda"}],"jpcoar:affiliationName":[{"@value":"Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School , Ann Arbor, MI 48109"},{"@value":"Department of Microbiology, Toho University School of Medicine , Tokyo ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380307543017180546","@type":"Researcher","foaf:name":[{"@value":"Jane C Deng"}],"jpcoar:affiliationName":[{"@value":"Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School , Ann Arbor, MI 48109"}]},{"@id":"https://cir.nii.ac.jp/crid/1380307543017180544","@type":"Researcher","foaf:name":[{"@value":"Thomas A Moore"}],"jpcoar:affiliationName":[{"@value":"Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School , Ann Arbor, MI 48109"}]},{"@id":"https://cir.nii.ac.jp/crid/1380307543017180545","@type":"Researcher","foaf:name":[{"@value":"Michael W Newstead"}],"jpcoar:affiliationName":[{"@value":"Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School , Ann Arbor, MI 48109"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895254941573","@type":"Researcher","foaf:name":[{"@value":"Robert Paine"}],"jpcoar:affiliationName":[{"@value":"Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School , Ann Arbor, MI 48109"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895254941568","@type":"Researcher","foaf:name":[{"@value":"Nobuyuki Kobayashi"}],"jpcoar:affiliationName":[{"@value":"Laboratory of Molecular Biology of Infectious Agents, Course of Emerging Infectious Diseases, Graduate School of Biomedical Science, Nagasaki University , Nagasaki ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895254941571","@type":"Researcher","foaf:name":[{"@value":"Keizo Yamaguchi"}],"jpcoar:affiliationName":[{"@value":"Department of Microbiology, Toho University School of Medicine , Tokyo ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380307543017180547","@type":"Researcher","foaf:name":[{"@value":"Theodore J Standiford"}],"jpcoar:affiliationName":[{"@value":"Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School , Ann Arbor, MI 48109"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00221767"},{"@type":"EISSN","@value":"15506606"}],"prism:publicationName":[{"@value":"The Journal of Immunology"}],"dc:publisher":[{"@value":"Oxford University Press (OUP)"}],"prism:publicationDate":"2003-04","prism:volume":"170","prism:number":"8","prism:startingPage":"4209","prism:endingPage":"4216"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","dc:rights":["https://academic.oup.com/pages/standard-publication-reuse-rights"],"url":[{"@id":"https://academic.oup.com/jimmunol/article-pdf/170/8/4209/62567837/4209.pdf"}],"createdAt":"2014-04-20","modifiedAt":"2026-02-02","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Inbred%20MRL%20lpr","dc:title":"Mice, Inbred MRL lpr"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Inbred%20A","dc:title":"Mice, Inbred A"},{"@id":"https://cir.nii.ac.jp/all?q=Tumor%20Necrosis%20Factor-alpha","dc:title":"Tumor Necrosis Factor-alpha"},{"@id":"https://cir.nii.ac.jp/all?q=Apoptosis","dc:title":"Apoptosis"},{"@id":"https://cir.nii.ac.jp/all?q=Epithelial%20Cells","dc:title":"Epithelial Cells"},{"@id":"https://cir.nii.ac.jp/all?q=Hyperoxia","dc:title":"Hyperoxia"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Inbred%20C57BL","dc:title":"Mice, Inbred C57BL"},{"@id":"https://cir.nii.ac.jp/all?q=Pulmonary%20Alveoli","dc:title":"Pulmonary Alveoli"},{"@id":"https://cir.nii.ac.jp/all?q=Survival%20Rate","dc:title":"Survival Rate"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Acute%20Disease","dc:title":"Acute Disease"},{"@id":"https://cir.nii.ac.jp/all?q=Pneumonia,%20Bacterial","dc:title":"Pneumonia, Bacterial"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Female","dc:title":"Female"},{"@id":"https://cir.nii.ac.jp/all?q=fas%20Receptor","dc:title":"fas Receptor"},{"@id":"https://cir.nii.ac.jp/all?q=Legionnaires'%20Disease","dc:title":"Legionnaires' Disease"},{"@id":"https://cir.nii.ac.jp/all?q=Lung","dc:title":"Lung"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004239880738816","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Metformin Mediates Protection against <i>Legionella</i> Pneumonia through Activation of AMPK and Mitochondrial Reactive Oxygen Species"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285710950729600","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Overlapping Roles for Interleukin-36 Cytokines in Protective Host Defense against Murine<i>Legionella pneumophila</i>Pneumonia"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567185928268800","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Roles of Interleukin-17 in an Experimental Legionella pneumophila Pneumonia Model"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001205051054464","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"A Case of <i>Legionella pneumophila</i> Pneumonia Accompanied by Acute Respiratory Distress Syndrome and Epilepsy"},{"@language":"ja","@value":"難治性癲癇患者に発症し，診断と抗菌薬選択に苦慮した Acute Respiratory Distress Syndrome（ARDS） 合併重症レジオネラ肺炎の 1 例"},{"@value":"症例 難治性癲癇患者に発症し,診断と抗菌薬選択に苦慮したAcute Respiratory Distress Syndrome (ARDS)合併重症レジオネラ肺炎の1例"},{"@language":"ja-Kana","@value":"ショウレイ ナンチセイ テンカン カンジャ ニ ハッショウ シ,シンダン ト コウキンヤク センタク ニ クリョ シタ Acute Respiratory Distress Syndrome (ARDS)ガッペイ ジュウショウ レジオネラ ハイエン ノ 1レイ"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282681421598336","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"5. 感染症治療の新たなる展開―基礎と臨床の接点を求めて―"},{"@language":"en","@value":"New development of infectious disease treatment. Search of the contact point of basic and clinical medicine"},{"@value":"招請講演 感染症治療の新たなる展開--基礎と臨床の接点を求めて"},{"@language":"ja-Kana","@value":"ショウセイ コウエン カンセンショウ チリョウ ノ アラタ ナル テンカイ キソ ト リンショウ ノ セッテン オ モトメテ"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.4049/jimmunol.170.8.4209"},{"@type":"OPENAIRE","@value":"doi_dedup___::e12aefd6cdc229afdcc6486896a1f9d8"},{"@type":"CROSSREF","@value":"10.4049/jimmunol.1700474_references_DOI_9JbEU9JOAWSZox0VrhHXJMp55Km"},{"@type":"CROSSREF","@value":"10.1128/iai.00583-18_references_DOI_9JbEU9JOAWSZox0VrhHXJMp55Km"},{"@type":"CROSSREF","@value":"10.2169/naika.95.1698_references_DOI_9JbEU9JOAWSZox0VrhHXJMp55Km"},{"@type":"CROSSREF","@value":"10.1128/iai.05544-11_references_DOI_9JbEU9JOAWSZox0VrhHXJMp55Km"},{"@type":"CROSSREF","@value":"10.11150/kansenshogakuzasshi.87.389_references_DOI_9JbEU9JOAWSZox0VrhHXJMp55Km"}]}