Published ahead of print on February 22, 2007, doi:10.1164/rccm.200602-161OC
© 2007 American Thoracic Society doi: 10.1164/rccm.200602-161OC
Plasma Cells and IL-4 in Chronic Bronchitis and Chronic Obstructive Pulmonary Disease1 Lung Pathology Unit, Department of Gene Therapy, Imperial College London at the Royal Brompton Hospital, London, United Kingdom; 2 Department of Clinical and Biological Sciences, University of Torino, Torino, Italy; and 3 King's College, University of Cambridge, Cambridge, United Kingdom Correspondence and requests for reprints should be addressed to Peter K. Jeffery, F.R.C.Path., D.Sc., Lung Pathology Unit, Department of Gene Therapy, Imperial College, London, at the Royal Brompton Hospital, Sydney St., London SW3 6NP, UK. E-mail: p.jeffery{at}imperial.ac.uk Rationale: Airway wall inflammation, IL-4, and mucus hypersecretion are thought to be associated. Objectives: To quantify bronchial inflammatory cells in smokers with chronic bronchitis (CB) with and without airflow obstruction (AO), determining the cells expressing IL-4 and IL-5 and their association with submucosal gland mucin. Methods: We applied immunohistochemistry to identify, and double-labeling to colocalize, IL-4 and IL-5 to distinct inflammatory cells in resected bronchi from (1) 11 asymptomatic smokers (AS), (2) 11 smokers with CB, and (3) 10 smokers with CB and AO. Measurements and Main Results: There were greater numbers of mucosal and gland CD45+ leukocytes in CB (epithelium, 673/mm2; subepithelium, 698/mm2; gland, 517/mm2) than in AS (331, 237, and 178/mm2, respectively; p < 0.01 for all) or CB + AO (375, 243, and 215/mm2, respectively; p < 0.05 for all). There were greater numbers of subepithelial and submucosal gland plasma cells in CB (subepithelium, 110/mm2; gland, 213/mm2) compared with AS (38 and 41/mm2, respectively; p < 0.01 for both), and more subepithelial mast cells in CB (204/mm2) than in AS (65/mm2; p < 0.01) or CB + AO (115/mm2; p < 0.01). In CB, the percentage of gland occupied by mucin was positively correlated with the numbers of interstitial CD45+ cells, plasma cells, and IL-4 protein+ cells. In CB, 69 and 62% of gland-associated plasma cells expressed IL-4 and IL-5, respectively. Conclusions: Inflammatory cells are increased in bronchial submucosal glands and mucosa of large airways in smokers with CB. Gland-associated plasma cells express IL-4, and these likely promote mucus hypersecretion.
Key Words: chronic bronchitis • chronic obstructive pulmonary disease • IL-4 • inflammation • plasma cells
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