{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:47:47Z","timestamp":1791654467410,"version":"4.3.4"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2001,5,1]],"date-time":"2001-05-01T00:00:00Z","timestamp":988675200000},"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":[[2001,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Eosinophil recruitment and enhanced production of NO are characteristic features of asthma. However, neither the ability of eosinophils to generate NO-derived oxidants nor their role in nitration of targets during asthma is established. Using gas chromatography-mass spectrometry we demonstrate a 10-fold increase in 3-nitrotyrosine (NO2Y) content, a global marker of protein modification by reactive nitrogen species, in proteins recovered from bronchoalveolar lavage of severe asthmatic patients (480 \u00b1 198 \u03bcmol\/mol tyrosine; n = 11) compared with nonasthmatic subjects (52.5 \u00b1 40.7 \u03bcmol\/mol tyrosine; n = 12). Parallel gas chromatography-mass spectrometry analyses of bronchoalveolar lavage proteins for 3-bromotyrosine (BrY) and 3-chlorotyrosine (ClY), selective markers of eosinophil peroxidase (EPO)- and myeloperoxidase-catalyzed oxidation, respectively, demonstrated a dramatic preferential formation of BrY in asthmatic (1093 \u00b1 457 \u03bcmol BrY\/mol tyrosine; 161 \u00b1 88 \u03bcmol ClY\/mol tyrosine; n = 11 each) compared with nonasthmatic subjects (13 \u00b1 14.5 \u03bcmol BrY\/mol tyrosine; 65 \u00b1 69 \u03bcmol ClY\/mol tyrosine; n = 12 each). Bronchial tissue from individuals who died of asthma demonstrated the most intense anti-NO2Y immunostaining in epitopes that colocalized with eosinophils. Although eosinophils from normal subjects failed to generate detectable levels of NO, NO2\u2212, NO3\u2212, or NO2Y, tyrosine nitration was promoted by eosinophils activated either in the presence of physiological levels of NO2\u2212 or an exogenous NO source. At low, but not high (e.g., &amp;gt;2 \u03bcM\/min), rates of NO flux, EPO inhibitors and catalase markedly attenuated aromatic nitration. These results identify eosinophils as a major source of oxidants during asthma. They also demonstrate that eosinophils use distinct mechanisms for generating NO-derived oxidants and identify EPO as an enzymatic source of nitrating intermediates in eosinophils.<\/jats:p>","DOI":"10.4049\/jimmunol.166.9.5763","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:42:04Z","timestamp":1398022924000},"page":"5763-5772","source":"Crossref","is-referenced-by-count":224,"title":["Eosinophils Are a Major Source of Nitric Oxide-Derived Oxidants in Severe Asthma: Characterization of Pathways Available to Eosinophils for Generating Reactive Nitrogen Species"],"prefix":"10.1093","volume":"166","author":[{"given":"Jennifer C","family":"MacPherson","sequence":"first","affiliation":[{"name":"Cell Biology, Cleveland Clinic Foundation , Cleveland, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzy A A","family":"Comhair","sequence":"additional","affiliation":[{"name":"Cancer Biology, Cleveland Clinic Foundation , Cleveland, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serpil C","family":"Erzurum","sequence":"additional","affiliation":[{"name":"Cancer Biology, Cleveland Clinic Foundation , Cleveland, OH 44195"},{"name":"Pulmonary and Critical Care Medicine, Cleveland Clinic Foundation , Cleveland, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis F","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of New Mexico School of Medicine , Albuquerque, NM 87131"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary F","family":"Lipscomb","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of New Mexico School of Medicine , Albuquerque, NM 87131"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mani S","family":"Kavuru","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine, Cleveland Clinic Foundation , Cleveland, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K","family":"Samoszuk","sequence":"additional","affiliation":[{"name":"Quest Diagnostics , San Juan Capistrano, CA 92690"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley L","family":"Hazen","sequence":"additional","affiliation":[{"name":"Cell Biology, Cleveland Clinic Foundation , Cleveland, OH 44195"},{"name":"Center for Cardiovascular Diagnostics, Cleveland Clinic Foundation , Cleveland, OH 44195"},{"name":"Cleveland State University, Department of Chemistry , Cleveland, OH 44115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2001,5,1]]},"reference":[{"key":"2026020209180143800_R1","first-page":"93","volume-title":"J. 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