{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:57:03Z","timestamp":1790773023112,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T00:00:00Z","timestamp":1312156800000},"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":[[2011,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The acceleration of chronic obstructive pulmonary disease (COPD) by cigarette smoke (CS) in individuals with severe genetic deficiency of \u03b11-antitrypsin (Z-AT [Glu342Lys]) exemplifies the critical importance of gene\u2013environmental interactions to the development of COPD. We investigated the molecular basis for the interaction between Z-AT and CS. Female mice (8\u201310 wk old) transgenic for normal (M-AT) or Z-AT on CBA background were exposed to four 1R3F cigarettes daily for 5 days. Age and sex matched littermates not exposed to CS were used as controls. Bronchoalveolar lavage fluid and lung homogenates were assessed for inflammatory cells, neutrophil elastase, and AT conformers. Z-AT was purified from plasma, exposed to CS extract, and assessed for the development and temporal relationship between AT conformers. Mice transgenic for Z-AT developed a significant increase in pulmonary polymers after acute CS exposure (P = 0.001). There were also increased neutrophils in CS-Z lungs versus controls (P &amp;lt; 0.001), which were tightly correlated with polymer concentrations (r2 = 0.93). Oxidation of human plasma Z-AT by CS or N-chlorosuccinimide greatly accelerated polymerization (P = 0.004), which could be abrogated by antioxidants (P = 0.359 versus Z control). Our data show that CS accelerates polymerization of Z-AT by oxidative modification, which, in so doing, further reduces pulmonary defense and increases neutrophil influx into the lungs. These novel findings provide a molecular explanation for the striking observation of premature emphysema in ZZ homozygotes who smoke. Further work is required to assess whether antioxidant therapy may be beneficial in Z-AT\u2013related COPD.<\/jats:p>","DOI":"10.1165\/rcmb.2010-0328oc","type":"journal-article","created":{"date-parts":[[2010,10,22]],"date-time":"2010-10-22T21:00:52Z","timestamp":1287781252000},"page":"261-269","source":"Crossref","is-referenced-by-count":110,"title":["Oxidation of Z \u03b11-Antitrypsin by Cigarette Smoke Induces Polymerization"],"prefix":"10.1093","volume":"45","author":[{"given":"Sam","family":"Alam","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenjun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge, United Kingdom; 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