title: Ovalbumin-induced airway inflammation and fibrosis in mice also exposed to ultrafine particles.
abstract: A murine model of allergen-induced airway inflammation was used to examine the effects of exposure to ultrafine particles (PM(2.5)) on airway inflammation and remodeling. Lung inflammation was measured by quantitative differential evaluation of lung lavage cells. Alterations in lung structure (airway remodeling and fibrosis) were evaluated by quantitative biochemical analysis of microdissected airways and by histological evaluation of stained lung sections. The same total number of cells was observed in lavage fluid from animals exposed for 4 wk to ovalbumin alone or to ovalbumin for 4 wk immediately before or after 6 exposures over a period of 2 wk to 235 ug/m(3) of PM(2.5). Mice exposed to ovalbumin for 6 wk with concurrent exposure to PM(2.5) during wk 5-6 had a significant decrease in the total number of cells recovered by lavage as compared with the group exposed to ovalbumin alone. There were no significant differences in the cell differential counts in the lavage fluid from mice exposed to ovalbumin alone as compared with values from mice exposed to ovalbumin and PM(2.5) under the protocols studied. Airway structural changes (remodeling) were examined by three different quantitative methods. None of the groups exposed to ovalbumin and PM had a significant increase in airway collagen content evaluated biochemically (i.e., total airway collagen) as compared to the matched groups of mice exposed to ovalbumin alone. Airway collagen content evaluated histologically by sirius red staining showed significant increases in all of the animals exposed to ovalbumin, with or without PM, and no apparent difference between the ovalbumin group and mice exposed to PM with ovalbumin. The findings were consistent with an additive, or less than additive, response of mice to exposure to PM and ovalbumin. Air or PM exposure alone for 2 wk did not result in observable goblet cells in the airways, while mice exposed to ovalbumin aerosol alone for 4 wk had about 20-25% goblet cells in their conducting airways. Sequential exposure to ovalbumin and PM (or vice versa) caused significant increases in goblet cells (to about 35% of total cells) in the conducting airways of the exposed mice. We conclude that when mice with allergen-induced airway inflammation induced by ovalbumin are also exposed to PM(2.5), the lung inflammatory response and airway remodeling may be modified, but that this altered response is dependent upon the sequence of exposure and the duration of exposure to ovalbumin aerosol. At the concentrations of PM tested, we did not see changes in airway fibrosis or airway reactivity for animals exposed to ovalbumin and PM(2.5) as compared with animals exposed only to ovalbumin aerosol. However, goblet-cell hyperplasia was significantly increased in mice exposed concurrently to ovalbumin and PM(2.5) as compared with mice exposed to ovalbumin alone.
authors.affiliation: Pulmonary and Critical Care Medicine, School of Medicine, and Center for Health and the Environment, University of California, Davis, California, USA. jalast@ucdavis.edu
authors.forename: Jerold A
authors.initials: JA
authors.lastname: Last
authors.forename: Rachel
authors.initials: R
authors.lastname: Ward
authors.forename: Lisa
authors.initials: L
authors.lastname: Temple
authors.forename: Kent E
authors.initials: KE
authors.lastname: Pinkerton
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Kenyon
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005355:Fibrosis; D006909:Hydroxyproline / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D019570:Inhalation Exposure; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology*; D010316:Particle Size; D013047:Specific Pathogen-Free Organisms
chemical_list: D000393:Air Pollutants; D010047:Ovalbumin; D003094:Collagen; D006909:Hydroxyproline