{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:12:36Z","timestamp":1792858356676,"version":"4.5.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T00:00:00Z","timestamp":1383264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Acute pulmonary infection by Streptococcus pneumoniae is characterized by high bacterial numbers in the lung, a robust alveolar influx of polymorphonuclear cells (PMNs), and a risk of systemic spread of the bacterium. We investigated host mediators of S. pneumoniae-induced PMN migration and the role of inflammation in septicemia following pneumococcal lung infection. Hepoxilin A3 (HXA3) is a PMN chemoattractant and a metabolite of the 12-lipoxygenase (12-LOX) pathway. We observed that S. pneumoniae infection induced the production of 12-LOX in cultured pulmonary epithelium and in the lungs of infected mice. Inhibition of the 12-LOX pathway prevented pathogen-induced PMN transepithelial migration in vitro and dramatically reduced lung inflammation upon high-dose pulmonary challenge with S. pneumoniae in vivo, thus implicating HXA3 in pneumococcus-induced pulmonary inflammation. PMN basolateral-to-apical transmigration in vitro significantly increased apical-to-basolateral transepithelial migration of bacteria. Mice suppressed in the expression of 12-LOX exhibited little or no bacteremia and survived an otherwise lethal pulmonary challenge. Our data suggest that pneumococcal pulmonary inflammation is required for high-level bacteremia and systemic infection, partly by disrupting lung epithelium through 12-LOX\u2013dependent HXA3 production and subsequent PMN transepithelial migration.<\/jats:p>","DOI":"10.4049\/jimmunol.1300522","type":"journal-article","created":{"date-parts":[[2013,10,3]],"date-time":"2013-10-03T01:17:19Z","timestamp":1380763039000},"page":"5115-5123","source":"Crossref","is-referenced-by-count":82,"title":["Systemic Disease during <i>Streptococcus pneumoniae<\/i> Acute Lung Infection Requires 12-Lipoxygenase\u2013Dependent Inflammation"],"prefix":"10.1093","volume":"191","author":[{"given":"Rudra","family":"Bhowmick","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University , Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nang H","family":"Tin Maung","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan P","family":"Hurley","sequence":"additional","affiliation":[{"name":"Mucosal Immunology Laboratory, Massachusetts General Hospital, Harvard Medical School , Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa Bou","family":"Ghanem","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University , Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Gronert","sequence":"additional","affiliation":[{"name":"Vision Science Program, School of Optometry, University of California, Berkeley , Berkeley, CA 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth A","family":"McCormick","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Physiological Systems, University of Massachusetts Medical School , Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M","family":"Leong","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University , Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,11,15]]},"reference":[{"key":"2025032405554428500_r1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1128\/JB.185.2.413-421.2003","article-title":"Transcriptional regulation in the Streptococcus pneumoniae rlrA pathogenicity islet by RlrA","volume":"185","author":"Hava","year":"2003","journal-title":"J. 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