title: Hyperresponsive airways correlate with lung tissue inflammatory cell changes in ozone-exposed rats.
abstract: The role of inflammatory cell infiltration in the development of hyperresponsiveness of the airways to muscarinic challenge remains poorly understood. Unlike previous investigations that only examined conducting airway inflammation, the present study utilized both bronchoalveolar lavage (BAL) and lung tissue digestion to determine rat lung inflammatory cell contents following a 4-h exposure to 2 ppm ozone. Immediately following ozone exposure, neutrophil content of the lung tissue was significantly increased and reached a value that was fourfold higher than air-exposed controls by 3 h postexposure. Although lavage-recovered neutrophils were elevated at 24 h, tissue neutrophil numbers had returned to control values. This transient elevation of tissue neutrophils directly correlated with an elevation and subsequent decline of airway hyperresponsiveness, measured as a decrease in the intravenous dose of methacholine provoking a 200% increase in airway resistance (PD(200)R). Animals rendered neutropenic with a rabbit anti-rat neutrophil serum prior to exposure were protected from ozone-induced hyperresponsive airways, further demonstrating an association between neutrophil infiltration into the lung and altered airway physiology. Although BAL-recovered neutrophils demonstrated no adverse effects as a result of ozone exposure, macrophages were not only found to be necrotic but also displayed altered oxidative metabolism when challenged with phorbol myristate acetate. Thus, changes in the microenvironment of the airways smooth muscle were shown to be associated with transient accumulation of neutrophils within the lung tissue and abnormalities of bronchoalveolar lavage-recovered macrophages.
authors.affiliation: Department of Occupational and Environmental Health Sciences, Wayne State University, Detroit, Michigan, USA. michael.p.delorme@usa.dupont.com
authors.forename: Michael P
authors.initials: MP
authors.lastname: DeLorme
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Constance
authors.initials: C
authors.lastname: Elbon-Copp
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Gao
authors.forename: Holly
authors.initials: H
authors.lastname: Barraclough-Mitchell
authors.forename: David J P
authors.initials: DJ
authors.lastname: Bassett
mesh_terms: D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016085:Bronchoconstrictor Agents; D002452:Cell Count; D017364:Collagenases / Q000378:metabolism; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016210:Methacholine Chloride; D009503:Neutropenia / Q000276:immunology / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D010126:Ozone / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms
chemical_list: D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D010126:Ozone; D017364:Collagenases