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 between pulmonary innate and adaptive immunity due to its antigen-presenting capacity and ability to express different immunomodulating mediators. The role of AMs in the pathogenesis of allergic inflammation has yet to be fully determined.


OBJECTIVE
To investigate clinical effects and any change in the AM phenotype pattern after inhalation of sub-clinical doses of allergen by asthmatic patients.


METHODS
Eight subjects with allergic asthma underwent repeated low-dose allergen provocations equivalent to 10% of PD20. AMs recovered with bronchoalveolar lavage (BAL) were characterized by flow cytometric analysis of adhesion molecules, co-stimulatory molecules and markers for AM population activation and heterogeneity.


RESULTS
An allergic airway inflammation, sub-clinical in six out of eight subjects, was obtained after low-dose allergen provocations, as determined by 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. The AMs were positive for CD83 and a weak post-challenge increase in the CD83 expression was found.


CONCLUSIONS
Repeated low-dose allergen exposure induces an allergic airway inflammation in asthmatic subjects. The inflammation is associated with an altered AM phenotype pattern, consistent with an influx of monocytes and a hypothetical increased accessory cell function in the airways, possibly contributing to the development and sustenance of airway inflammation in asthma.
Lensmar
C
C
Department of Medicine, Division of Respiratory Medicine, Karolinska Hospital and Karolinska Institutet, Stockholm, Sweden.
Prieto
J
J
Dahlén
B
B
Eklund
A
A
Grunewald
J
J
Roquet
A
A
D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001798:Blood Proteins; D016535:Bronchial Hyperreactivity; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology* / Q000276:immunology; D047091:Eosinophil Granule Proteins; D004804:Eosinophils; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007249:Inflammation; D016676:Macrophages, Alveolar / Q000145:classification / Q000276:immunology*; D008297:Male; D016210:Methacholine Chloride; D006109:Poaceae / Q000276:immunology; D011058:Pollen; D012260:Ribonucleases; D014197:Trees / Q000276:immunology
D000485:Allergens; D000911:Antibodies, Monoclonal; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D016210:Methacholine Chloride; D012260:Ribonucleases