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Published ahead of print on August 25, 2005, doi:10.1165/rcmb.2005-0124OC

Am. J. Respir. Cell Mol. Biol., Volume 33, Number 6, December 2005, 531-540

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Submitted on April 5, 2005
Revised on August 19, 2005

Localization and Up-regulation of Cysteinyl Leukotriene-1 Receptor in Asthmatic Bronchial Mucosa

Jie Zhu1, Yu-Sheng Qiu1, David J Figueroa2, Venkata Bandi3, Helen Galczenski2, Kaoru Hamada4, Kalpalatha K Guntupalli3, Jilly F Evans2, and Peter Key Jeffery1*

1 Department of Gene Therapy, Imperial College London, London, London, United Kingdom, 2 Merck Research Laboratories, Merck and Co. Inc., Rahway, New Jersey, USA, 3 Department of Medicine, Baylor College of Medicine, Houston, Texas, USA, 4 Department of Respiratory Medicine, Nara Medical University, Nara, Japan

* To whom correspondence should be addressed. 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-labelling 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 non-smoker non-atopic non-asthma controls 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 hospitalised 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 sub-groups, 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.




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