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Published ahead of print on February 22, 2007, doi:10.1164/rccm.200602-161OC

Am. J. Respir. Crit. Care Med., Volume 175, Number 11, June 2007, 1125-1133

A more recent version of this article appeared on June 1, 2007
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Submitted on February 3, 2006
Accepted on February 22, 2007

Plasma Cells and Interleukin-4 in Chronic Bronchitis and COPD

Jie Zhu1, Yusheng Qiu1, Monica Valobra2, Shengyang Qiu3, Swati Majumdar1, Dean Matin1, Virginia De Rose2, and Peter K Jeffery1*

1 Lung Pathology, 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, 3 Lung Pathology, Gene Therapy, Imperial College London at the Royal Brompton Hospital, London, United Kingdom; King's College, University of Cambridge, Cambridge, United Kingdom

* To whom correspondence should be addressed. E-mail: p.jeffery{at}imperial.ac.uk.

Hypothesis: Airway wall inflammation, interleukin (IL)-4 and mucus-hypersecretion are associated. Objectives: To quantify bronchial inflammatory cells in chronic bronchitic smokers 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-labelling to colocalize, IL-4 and IL-5 to distinct inflammatory cells in resected bronchi from: (1) 11 asymptomatic smokers (AS), (2) 11 smokers with chronic bronchitis alone (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 mm-2, subepithelium: 698 mm-2, gland: 517 mm-2) than in AS (331, 237 and 178 mm-2; respectively; P<0.01 for all) or CB + AO (375, 243 and 215 mm-2, respectively; P<0.05 for all). There were greater numbers of subepithelial and submucosal gland plasma cells in CB (subepithelium: 110 mm-2, gland: 213 mm-2), compared with AS (38 and 41 mm-2; respectively; p<0.01 for both) and more subepithelial mast cells in CB (204 mm-2) than AS (65 mm-2, p<0.01) or CB + AO (115 mm-2, 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. Conclusion: 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: Plasma cells, inflammation, interleukin-4, chronic bronchitis, COPD




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