Plasma cells and IL-4 in chronic bronchitis and chronic obstructive pulmonary disease.
BACKGROUND
Airway wall inflammation, IL-4, and mucus hypersecretion are thought to be associated.


OBJECTIVE
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.


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 in 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.


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.
Zhu
Jie
J
Lung Pathology Unit, Department of Gene Therapy, Imperial College London at the Royal Brompton Hospital, Sydney St., London SW3 6NP, UK.
Qiu
Yusheng
Y
Valobra
Monica
M
Qiu
Shengyang
S
Majumdar
Swati
S
Matin
Dean
D
De Rose
Virginia
V
Jeffery
Peter K
PK
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D029481:Bronchitis, Chronic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics*; D015848:Interleukin-5 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000276:immunology; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism; D009093:Mucus / Q000166:cytology / Q000378:metabolism; D010950:Plasma Cells / Q000473:pathology*; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018075:RNA, Complementary / Q000235:genetics*; D012720:Severity of Illness Index
D015415:Biomarkers; D015848:Interleukin-5; D009077:Mucins; D018075:RNA, Complementary; D015847:Interleukin-4; D017493:Leukocyte Common Antigens