Published ahead of print on February 15, 2007, doi:10.1164/rccm.200607-908OC
Am. J. Respir. Crit. Care Med., Volume 175, Number 9, May 2007, 919-925
A more recent version of this article appeared on May 1, 2007
Submitted on July 5, 2006
Accepted on February 12, 2007
Cigarette Smoking Alters Bronchial Mucosal Immunity in Asthma
Maria Tsoumakidou1, William Elston2, Jie Zhu3, Zhuo Wang3, Elizabeth Gamble4, Nikolaos M Siafakas5, Neil C Barnes6, and Peter K Jeffery3*
1 Department of Gene Therapy, Imperial College London, Lung Pathology Uniit, London, United Kingdom; Thoracic Medicine, University of Crete, Crete, Greece,
2 Department of Gene Therapy, Imperial College London, Lung Pathology Uniit, London, United Kingdom; Respiratory Medicine, St Barts and the London Hospital Trust, London, United Kingdom,
3 Department of Gene Therapy, Imperial College London, Lung Pathology Uniit, London, United Kingdom,
4 Respiratory Medicine, Bristol Royal Infirmary, Bristol, Bristol, United Kingdom,
5 Thoracic Medicine, University of Crete, Crete, Greece,
6 Respiratory Medicine, St Barts and the London Hospital Trust, London, United Kingdom
* To whom correspondence should be addressed. E-mail: p.jeffery{at}imperial.ac.uk.
Rationale: Cigarette smoking worsens asthma and is associated with a reduced response to corticosteroid therapy. As cigarette smoke is known to have immunomodulatory effects, we hypothesize that one mechanism by which smoking mediates its adverse effect is by reduction of the numbers of bronchial mucosal dendritic cells (DCs), which control B-cell growth and T-cell responses.
Objectives: We set out to sample the bronchial mucosa in smoking and never-smoking asthmatics and count DCs, B-cells and cells expressing genes for two key T-lymphocyte regulatory cytokines.
Methods: Twenty-one never-smoker asthmatics (6 steroid-naive), 24 smoker asthmatics (9 steroid-naive) and 10 healthy never-smokers (controls) were recruited and their endobronchial biopsies immunostained for detection of mature DCs (CD83+), Langerhan's cells (CD1a+), B lymphocytes (CD20+), Th1 (IFN ) and Th2 (IL-4) cytokine expressing cells.
Measurements and main results: The number (per mm2) of CD83+ve mature DCs was significantly lower in smoker [median(range)] [37(0,131)] by comparison with never-smoker steroid-naive and steroid-treated asthmatics [76(24,464); p=0.006] or controls [85(40,294); p=0.004]. Moreover, B cells were fewer in smoker [26(4,234)] versus never-smoker steroid-naive and steroid-treated asthmatics [45(10,447); p=0.01] and in smoker steroid-naive asthmatics [23(4,111)] versus controls [34(10,130); p=0.05]. The number of cells expressing IFN showed a trend to fewer in smoker [70(6,24)] versus never-smoker steroid-naive asthmatics [144(44,323); p=0.10].
Conclusions: There are important and statistically significant differences in the number of CD83+ mature DCs and B cells in the large airways of smokers with asthma. We speculate that their reductions may render asthmatics less responsive to corticosteroids and more susceptible to infection.
Key words: asthmatic; smoker; inflammation; dendritic cells; lymphocytes
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