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Copyright ©ERS Journals Ltd 2004
Expression of HCLCA1 in cystic fibrosis lungs is associated with mucus overproduction
1 Meakins-Christie Laboratories, McGill University, Montreal, Canada. 2 U416 INSERM, Institut Pasteur de Lille and Centre de Soins Mucoviscidose Adulte, Hôpital Calmatte, Lille, France. 3 Royal College of Surgeons, Dublin, Ireland. 4 Montreal Chest Hospital, Montreal, Canada. 5 Genaera Corporation, Plymouth Meeting, USA
CORRESPONDENCE: Q. Hamid, Meakins-Christie Laboratories, 3626 St-Urbain Street, Montreal, Quebec, Canada. Fax: 1 5143987483. E-mail: qutayba.hamid@mcgill.ca
Keywords: Cystic fibrosis, hCLCA1, interleukin-9, mucus
Received: August 22, 2003
Accepted December 17, 2003
This work was supported by the Genaera Corporation and the Canadian Institutes of Health Research, Canada. H.P. Hauber is the recipient of a grant from the Christiane-Herzog Stiftung.
Mucus overproduction is typical in cystic fibrosis (CF) airway disease. The human calcium-activated chloride channel, hCLCA1, has been reported to be upregulated by interleukin (IL)-9 and to regulate the expression of mucins. Therefore, the expression of IL-9, IL-9 receptor (IL-9R) and hCLCA1 between the lungs of CF patients and healthy control subjects was compared.
Endoscopic biopsy samples of bronchial mucosa from 10 CF patients and six control subjects were stained with periodic acid-Schiff. IL-9, IL-9R and hCLCA1 expression was determined by immunocytochemistry. Expression of hCLCA1 mRNA was also determined by in situ hybridisation.
The present study found significant increases in IL-9, IL-9R and hCLCA1 immunoreactivity, hCLCA1 mRNA expression, and numbers of mucus-producing cells in the mucosa of CF patients compared to control subjects. Positive correlations were found between IL-9R-positive-cells with IL-9-positive cells and hCLCA1-positive cells, and between PAS-positive cells with hCLCA1-positive cells and IL-9R-positive cells. Expression of hCLCA1 mRNA was colocalised with IL-9R expression and PAS-positive staining in epithelial cells.
Increased expression of interleukin-9 and interleukin-9 receptor, as well as an upregulation of the human calcium-activated chloride channel, hCLCA1, in mucus-producing epithelium of cystic fibrosis patients, support the hypothesis that interleukin-9 contributes to mucus overproduction in cystic fibrosis airway disease.
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