title: Time course of neutrophil and macrophage elastinolytic activities in cigarette smoke-induced emphysema.
abstract: The aim of this study was to compare the time course of neutrophil and macrophage elastinolytic potentials in the lungs of rats exposed daily to cigarette smoke inhalation for 1-6 mo in relation to the onset and progression of cigarette smoke-induced emphysema. Normal room air-exposed rats served as controls. Morphometric data of lung histological sections showed evidence of emphysema lesions in the lungs of smoke-exposed rats at month 2 and continuing to month 6. Data of total and differential cell counts in bronchoalveolar lavage fluid and collagenase-dissociated lung showed an increased number of lung neutrophils at month 1 of smoke exposure, but this was reduced to control levels at months 2-6. In contrast, an increased number of lung macrophages was evident in the smoke-exposed rats at month 2 of exposure and continued to month 6. Data of the elastinolytic activities of the neutrophils and macrophages, determined in [3H]elastin-coated culture wells, showed that the elastinolytic activity of lung neutrophils in the smoke-exposed rats was similar to that of the control air-exposed rats at months 1-6 of exposure. In contrast, the elastinolytic activity of lung macrophages in the smoke-exposed rats was increased at month 2 of exposure and remained increased at month 6. Excessive in vivo lung elastin breakdown (judged by increased levels of elastin-derived peptides and desmosine in lavage fluid, determined immunologically) was observed in the smoke-exposed rats at months 2-6 of exposure. These data indicate that the time course of increased macrophage-directed elastinolytic activity in the lung, not that of neutrophils, is more closely associated with the evolution of cigarette smoke-induced emphysema.
authors.affiliation: Respiratory Division, Department of Medicine, University of British Columbia and Vancouver General Hospital, Vancouver, British Columbia, Canada V6H 3Z6.
authors.forename: A F
authors.initials: AF
authors.lastname: Ofulue
authors.forename: M
authors.initials: M
authors.lastname: Ko
authors.forename: R T
authors.initials: RT
authors.lastname: Abboud
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004549:Elastin / Q000378:metabolism*; D007958:Leukocyte Count; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000473:pathology / Q000502:physiology*; D008297:Male; D009504:Neutrophils / Q000473:pathology / Q000502:physiology*; D011656:Pulmonary Emphysema / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012907:Smoking; D013997:Time Factors
chemical_list: D004549:Elastin