{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T07:29:08Z","timestamp":1792740548443,"version":"4.5.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[1999,4,1]],"date-time":"1999-04-01T00:00:00Z","timestamp":922924800000},"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":[[1999,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Toluene diisocyanate (TDI) is a low-molecular-weight compound which is known to cause occupational asthma in 5 to 10% of exposed workers. Previously, we developed a murine model to investigate TDI-induced occupational asthma. Short-term exposure to TDI (skin sensitization twice daily on Day 0 and Day 1 and intranasal challenge on Day 8) led to a nonspecific tracheal hyperractivity 24 h after the challenge in TDI-sensitized mice when compared with nonsensitized mice whereas no TDI-specific IgE antibodies were found in the serum. Because 20% of subjects with TDI-induced occupational asthma exhibit an increase in serum IgE antibodies, we exposed mice for a longer period of time to investigate whether this procedure could induce TDI-specific antibody production in exposed mice. Long-term exposure (skin sensitization on 6 consecutive weeks followed by intranasal challenge on Week 7) resulted in the production of total IgE and IgG and TDI-specific IgE and IgG antibodies. Airway reactivity to various agonists was also measured in vitro and in vivo in long-term exposed mice. TDI-sensitized mice exhibited in vitro tracheal hyperreactivity to carbachol 3 h after the challenge when compared with the nonsensitized mice. Moreover, in vivo airway hyperresponsiveness to serotonin (5-hydroxytryptamine [5HT]) was found 3 h after the challenge in TDI-sensitized mice. Interestingly, in vivo airway hyperresponsiveness was not observed at any time point in the mice exposed to TDI according to the short-term protocol. In conclusion, by altering the exposure time and\/or cumulative dosage of TDI different biological reactions can be elicited in exposed mice. This important finding might be a reflection of the diversity of symptoms found in patients suffering from TDI-induced asthma. Both the short-exposure and the long-exposure model will be useful to further investigate the mechanisms of action of TDI.<\/jats:p>","DOI":"10.1164\/ajrccm.159.4.9701012","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T13:53:06Z","timestamp":1365083586000},"page":"1074-1080","source":"Crossref","is-referenced-by-count":55,"title":["Long-term Topical Exposure to Toluene Diisocyanate in Mice Leads to Antibody Production and\n                    <i>In Vivo<\/i>\n                    Airway Hyperresponsiveness Three Hours after Intranasal Challenge"],"prefix":"10.1093","volume":"159","author":[{"given":"HELEEN","family":"SCHEERENS","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht; and National Institute of Public Health and the Environment, Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"THERESA L.","family":"BUCKLEY","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht; and National Institute of Public Health and the Environment, Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"THEA LEUSINK","family":"MUIS","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht; and National Institute of Public Health and the Environment, Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JOHAN","family":"GARSSEN","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht; and National Institute of Public Health and the Environment, Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JAN","family":"DORMANS","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht; and National Institute of Public Health and the Environment, Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FRANS P.","family":"NIJKAMP","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht; and National Institute of Public Health and the Environment, Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HENK","family":"VAN LOVEREN","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht; and National Institute of Public Health and the Environment, Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1999,4,1]]},"reference":[{"key":"2026032708533741400_B1","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1378\/chest.103.4.1123","article-title":"Bronchial hyperresponsiveness and toluene diisocyanate.","volume":"103","author":"Paggiaro","year":"1993","journal-title":"Chest"},{"key":"2026032708533741400_B2","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1164\/ajrccm.149.3.8118626","article-title":"Predictive value of airways hyperresponsiveness and circulating IgE for identifying types of responses to toluene diisocyanate inhalation challenge.","volume":"149","author":"Karol","year":"1994","journal-title":"Am. 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