{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:39:42Z","timestamp":1791877182422,"version":"4.3.4"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,4,30]],"date-time":"2014-04-30T00:00:00Z","timestamp":1398816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological sciences Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Neutrophil extracellular traps (<jats:styled-content style=\"fixed-case\">NET<\/jats:styled-content>s) are a recently discovered addition to the defensive armamentarium of neutrophils, assisting in the immune response against rapidly dividing bacteria. Although older adults are more susceptible to such infections, no study has examined whether aging in humans influences <jats:styled-content style=\"fixed-case\">NET<\/jats:styled-content> formation. We report that <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1\u2010primed neutrophils generate significantly more <jats:styled-content style=\"fixed-case\">NET<\/jats:styled-content>s than unprimed neutrophils and that lipopolysaccharide (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>)\u2010 and interleukin\u20108 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108)\u2010induced <jats:styled-content style=\"fixed-case\">NET<\/jats:styled-content> formation exhibits a significant age\u2010related decline. <jats:styled-content style=\"fixed-case\">NET<\/jats:styled-content> formation requires generation of reactive oxygen species (<jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>), and this was also reduced in neutrophils from older donors identifying a mechanism for reduced <jats:styled-content style=\"fixed-case\">NET<\/jats:styled-content> formation. Expression of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 receptors (<jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>1 and <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>2) and the <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> receptor <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 was similar on neutrophils from young and old subjects, and neutrophils challenged with phorbol\u201012\u2010myristate\u201013\u2010acetate (<jats:styled-content style=\"fixed-case\">PMA<\/jats:styled-content>) showed no age\u2010associated differences in <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">NET<\/jats:styled-content> production. Taken together, these data suggest a defect in proximal signalling underlies the age\u2010related decline in <jats:styled-content style=\"fixed-case\">NET<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> generation. <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1 priming involves signalling through p38 <jats:styled-content style=\"fixed-case\">MAP<\/jats:styled-content> kinase, but activation kinetics were comparable in neutrophils from young and old donors. In a clinical setting, we assessed the capacity of neutrophils from young and older patients with chronic periodontitis to generate <jats:styled-content style=\"fixed-case\">NET<\/jats:styled-content>s in response to <jats:styled-content style=\"fixed-case\">PMA<\/jats:styled-content> and hypochlorous acid (<jats:styled-content style=\"fixed-case\">HOCL<\/jats:styled-content>). Neutrophil extracellular trap generation to <jats:styled-content style=\"fixed-case\">HOCL<\/jats:styled-content>, but not <jats:styled-content style=\"fixed-case\">PMA<\/jats:styled-content>, was lower in older periodontitis patients but not in comparison with age\u2010matched controls. Impaired <jats:styled-content style=\"fixed-case\">NET<\/jats:styled-content> formation is thus a novel defect of innate immunity in older adults but does not appear to contribute to the increased incidence of periodontitis in older adults.<\/jats:p>","DOI":"10.1111\/acel.12222","type":"journal-article","created":{"date-parts":[[2014,4,30]],"date-time":"2014-04-30T06:03:54Z","timestamp":1398837834000},"page":"690-698","source":"Crossref","is-referenced-by-count":269,"title":["Impaired neutrophil extracellular trap formation: a novel defect in the innate immune system of aged individuals"],"prefix":"10.1111","volume":"13","author":[{"given":"Jon","family":"Hazeldine","sequence":"first","affiliation":[{"name":"MRC\u2010ARUK Centre for Musculoskeletal Ageing Research School of Immunity and Infection Birmingham University Medical School Birmingham B15 2TT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillipa","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Dentistry University of Birmingham Birmingham B15 2TT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain L.","family":"Chapple","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Dentistry University of Birmingham Birmingham B15 2TT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Grant","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Dentistry University of Birmingham Birmingham B15 2TT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Greenwood","sequence":"additional","affiliation":[{"name":"School of Clinical and Experimental Medicine The Medical School University of Birmingham Birmingham B15 2TT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Livesey","sequence":"additional","affiliation":[{"name":"MRC\u2010ARUK Centre for Musculoskeletal Ageing Research School of Immunity and Infection Birmingham University Medical School Birmingham B15 2TT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Sapey","sequence":"additional","affiliation":[{"name":"School of Clinical and Experimental Medicine The Medical School University of Birmingham Birmingham B15 2TT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet M.","family":"Lord","sequence":"additional","affiliation":[{"name":"MRC\u2010ARUK Centre for Musculoskeletal Ageing Research School of Immunity and Infection Birmingham University Medical School Birmingham B15 2TT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,4,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)36655-4"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-05-221606"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385"},{"key":"e_1_2_8_5_1","first-page":"1724","article-title":"Neutrophil extracellular traps: how to generate and visualize them","volume":"36","author":"Brinkmann V","year":"2010","journal-title":"J. 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