Airway inflammation and altered alveolar macrophage phenotype pattern after repeated low-dose allergen exposure of atopic asthmatic subjects

Background The alveolar macrophage (AM) constitutes an important link betwe en pulmonary innate and adaptive immunity due to its antigen-presenting cap acity and ability to express different immunomodulating mediators. The role of AMs in the pathogenesis of allergic inflammation has yet to be fully de termined. Objective To investigate clinical effects and any change in the AM phenotyp e pattern after inhalation of sub-clinical doses of allergen by asthmatic p atients. Methods Eight subjects with allergic asthma underwent repeated low-dose all ergen provocations equivalent to 10% of PD20. AMs recovered with bronchoalv eolar lavage (BAL) were characterized by flow cytometric analysis of adhesi on molecules, co-stimulatory molecules and markers for AM population activa tion and heterogeneity. Results An allergic airway inflammation, sub-clinical in six out of eight s ubjects, was obtained after low-dose allergen provocations, as determined b y increased airway methacholine reactivity, increased BAL fluid total cell and eosinophil counts and increased serum ECP levels. The AMs showed a post -challenge altered phenotype pattern with a decreased expression of CD11a, CD16, CD71 and HLA class I and an increased expression of CD11b and CD14. T he AMs were positive for CD83 and a weak post-challenge increase in the CD8 3 expression was found. Conclusion Repeated low-dose allergen exposure induces an allergic airway i nflammation in asthmatic subjects. The inflammation is associated with an a ltered AM phenotype pattern, consistent with an influx of monocytes and a h ypothetical increased accessory cell function in the airways, possibly cont ributing to the development and sustenance of airway inflammation in asthma .