Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 177, Issue 4, Pages 1657-1664Publisher
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2010.100019
Keywords
-
Categories
Funding
- National Health and Medical Research Council of Australia
Ask authors/readers for more resources
The mechanisms underlying the exaggerated distal airway inflammation and hyperresponsiveness that characterize acute exacerbations of asthma are largely unknown. Using BALB/c mouse experimental models, we demonstrated a potentially important role for alveolar macrophages (AM) in the development of an allergen-induced exacerbation of asthma. To induce features of airway inflammation and remodeling characteristic of mild chronic asthma, animals were systemically sensitized and exposed to low mass concentrations (approximate to 3 mg/m(3)) of aerosolized ovalbumin for 30 minutes per day, 3 days per week, for 4 weeks. A subsequent single moderate-level challenge (approximate to 30 mg/m(3)) was used to trigger an acute exacerbation. In chronically challenged animals, cytokine expression by AM was not increased, whereas after an acute exacerbation, AM exhibited significantly enhanced expression of proinflammatory cytokines, including interleukin (IL) 1 beta, IL-6, CXCL-1, and tumor necrosis factor a. In parallel, there was a marked increase in the expression of several cytokines by CD4(+) T-lymphocytes, notably the Th2 cytokines IL-4 and IL-13. Importantly, AM from an acute exacerbation stimulated the expression of Th2 cytokines when cocultured with CD4(+) cells from chronically challenged animals, and their ability to do so was significantly greater than AM from either chronically challenged or naive controls. Stimulation was partly dependent on interactions involving CD80/86. We conclude that in an acute exacerbation of asthma, enhanced cytokine expression by AM may play a critical role in triggering increased expression of cytokines by pulmonary CD4(+) T-lymphocytes. (Am J Pathol 2010, 177:1657-1664; DOI: 10.2353/ajpath.2010.100019)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available