Published ahead of print on August 25, 2005, doi:10.1165/rcmb.2005-0124OC
© 2005 American Thoracic Society DOI: 10.1165/rcmb.2005-0124OC Localization and Upregulation of Cysteinyl Leukotriene-1 Receptor in Asthmatic Bronchial MucosaImperial College London at the Royal Brompton Hospital, London, United Kingdom; Merck & Co., Inc., West Point, Pennsylvania; Baylor College of Medicine, Houston, Texas; and Nara Medical University, Nara, Japan Correspondence and requests for reprints should be addressed to Professor Peter K. Jeffery, Lung Pathology, Imperial College London, Royal Brompton Hospital, Sydney Street, London SW3 6NP, United Kingdom. E-mail: p.jeffery{at}imperial.ac.uk We have tested the hypothesis that the CysLT1 receptor is expressed by a variety of bronchial mucosal immune cells and that the numbers of these cells increase in asthma, when stable and in exacerbations. We have applied in situ hybridization and immunohistochemistry to endobronchial biopsy tissue to identify and count inflammatory cells expressing CysLT1 receptor mRNA and protein, respectively, and used double immunohistochemistry to identify the specific cell immunophenotypes expressing the receptor. Double-labeling demonstrated that bronchial mucosal eosinophils, neutrophils, mast cells, macrophages, B-lymphocytes, and plasma cells, but not T-lymphocytes, expressed the CysLT1 receptor. The numbers of CysLT1 receptor mRNA and protein positive inflammatory cells in nonsmoking, nonatopic control subjects without asthma were 13 and 16 mm–2, respectively (median values; n = 15), and were significantly greater in stable asthma (50 and 43 mm–2, respectively; n = 17; P < 0.001). Compared with stable asthma, there were further significant increases in subjects hospitalized for a severe exacerbation of their asthma (mRNA: median = 113 and protein: 156 mm–2; n = 15; P < 0.002). For the combined data of both asthma subgroups, there were strong positive correlations between the increased numbers of CD45+ leukocytes and the greater numbers of cells expressing CysLT1 receptor (mRNA: r = 0.60, P < 0.001; protein: r = 0.73, P < 0.0001). In conclusion, a variety of immunohistologically distinct inflammatory cells express the CysLT1 receptor in the bronchial mucosa and both these and the total number of leukocytes increase in mild stable disease and increase further when there is a severe exacerbation of asthma.
Key Words: asthma • cysteinyl leukotrienes • exacerbation • receptor This article has been cited by other articles:
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