EFFECTS OF ENVIRONMENTAL AEROSOLS ON AIRWAY HYPERRESPONSIVENESS IN A MURINE MODEL OF ASTHMA
Authors: Goldsmith, Carroll-Ann W.; Hamada, Kaoru; Ning, Yaoyu; Qin, Guozhong; Catalano, Paul; Murthy, G. G. Krishna; Lawrence, Joy; Kobzik, Lester
Source: Inhalation Toxicology, Volume 11, Number 11, 1 November 1999 , pp. 981-998(18)
Publisher: Informa Healthcare
Abstract:Increased morbidity in persons suffering from inflammatory lung diseases, such as asthma and bronchitis, has been associated with air pollution particles. One hypothesis is that particles can cause an amplification of the pulmonary inflammation associated with these diseases, thus worsening affected individuals' symptoms. This hypothesis was tested in a murine model of asthma by inhalation exposure to (1) concentrated air particles (CAPs), (2) the leachate of residual oil fly ash (ROFA-S), and (3) lipopolysaccharide (LPS). Allergen-sensitized mice (ip ovalbumin, OVA) were 21 days old when challenged with an aerosol of 3% OVA in phosphate-buffered saline (PBS) for 10 min (controls were challenged with PBS only) for 3 days. On the same days, mice were further exposed to 1 of 3 additional agents: CAPs (or filtered air) for 6 h/day; LPS (5 mug/ml, or PBS) for 10 min/day; or ROFA-S (leachate of 50 mg/ml, or PBS) for 30 min on day 2 only. At 24 h later, mice challenged with OVA aerosol showed airway inflammation and airway hyperresponsiveness (AHR) to methacholine (Mch), features absent in mice challenged with PBS alone. Both OVA- and PBS-challenged mice subsequently exposed to ROFA-S showed increased AHR to Mch when compared to their respective controls (OVA only or PBS only). In contrast, when OVA-challenged mice were further exposed to CAPs or LPS, no changes in AHR were seen in comparison to mice challenged with OVA only. Bronchoalveolar lavage (BAL) analysis and histopathology 48 h postexposure showed OVA-induced allergic inflammation. No significant additional effects were caused by CAPs or ROFA-S. LPS, in contrast, caused significant increases in total cell, macrophage, and polymorphonuclear cell numbers. The data highlight discordance between airway inflammation and hyperresponsiveness.
Document Type: Research Article
Publication date: 1999-11-01