Upregulation of αGM-CSF-receptor in nonatopic asthma but not in atopic asthma☆,☆☆,★,★★

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Abstract

Background: Intrinsic asthma is characterized by an increased number of activated eosinophils and macrophages and an increased expression of the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) in the bronchial mucosa. Objective: This study was carried out to investigate the expression of αGM-CSF receptor (αGM-CSFr) messenger RNA and protein in the bronchial mucosa of patients with intrinsic or atopic asthma and of control subjects and to correlate the expression of αGM-CSFr to the number of EG2+ cells (eosinophils) and CD68+ cells (macrophages) and pulmonary function. Methods: Nineteen patients with stable asthma (9 with atopic and 10 with intrinsic asthma) and 22 normal control subjects (12 atopic and 10 nonatopic subjects) were recruited, and FEV1 (percent predicted) and PC20 were measured before bronchoscopy. Endobronchial biopsy specimens were obtained and examined for membrane-bound αGM-CSFr by using in situ hybridization and immunocytochemistry. Results: αGM-CSFr mRNA- and protein-positive cells were identified in biopsy specimens from all four groups studied. There was no significant difference in the number of cells expressing αGM-CSFr mRNA and protein in patients with atopic asthma compared with atopic and nonatopic control subjects. However, the numbers of αGM-CSFr mRNA- and protein-positive cells were significantly higher in nonatopic patients with asthma compared with atopic patients with asthma and atopic and nonatopic control subjects (p < 0.001). In the patients with intrinsic asthma, the number of αGM-CSFr mRNA-positive cells per millimeter of basement membrane correlated with numbers of CD68+ cells (r2 = 0.87, p < 0.001) but not with EG2 + cells, and colocalization studies demonstrated that 80% of the cells expressing αGMCSFr mRNA were CD68+. The expression of GM-CSF was also significantly increased in patients with intrinsic asthma compared with those with atopic asthma and control subjects ( p  < 0.05). In addition, in intrinsic asthma, there was a correlation between αGM-CSFr mRNA and FEV1 ( r2 = 0.61, p < 0.05). Conclusion: These results demonstrate that elevated numbers of cells expressing αGM-CSFr can be detected in nonatopic asthma but not in atopic asthma and suggest that this increased expression is predominantly macrophage-associated and may play an important pathophysiologic role in intrinsic asthma. (J Allergy Clin Immunol 1997;99:666-72.)

Section snippets

Subjects

Bronchial biopsy specimens from 19 patients with stable asthma (9 with atopic asthma; and 10 with intrinsic asthma) and 22 control subjects (12 atopic and 10 nonatopic subjects) were obtained. The patients studied were recruited from the Allergy Clinic at the Royal Brompton National Heart and Lung Hospital, London, U.K., and the Department of Pneumonology II, Hochgebirsgklink, Davos Wolfgang, Switzerland. The diagnoses of asthma and atopy were as previously described.13 In brief, all the

RESULTS

Nineteen patients with stable asthma (9 with atopic and 10 with intrinsic asthma) and 22 control subjects (12 atopics and 10 nonatopic subjects) were studied. The median ages of the four groups of subjects were as follows: nonatopic control subjects, 22 years (range, 19 to 39 years); atopic control subjects, 24.5 years (range, 21 to 42 years); patients with atopic asthma, 26 years (range, 23 to 42 years) and; patients with nonatopic asthma, 53.5 years (range, 39 to 62 years). The asthmatic

DISCUSSION

This study provides the first conclusive evidence of the upregulation of αGM-CSFr in the bronchial biopsy specimens of asthmatic subjects compared with those from control subjects. The results demonstrate that there are elevated numbers of αGM-CSFr mRNA– and protein–positive cells in nonatopic asthma but not in atopic asthma. We have also shown that the increased expression for αGM-CSFr is associated with an increased expression of GM-CSF and that the majority of αGM-CSFr–positive cells are

Acknowledgements

We thank Elsa Schotman, Zivart Yasruel, and Marie Plourde for their invaluable technical assistance.

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    • Cited by (0)

    ☆

    From athe Meakins-Christie Laboratories, McGill University, Montreal, Quebec; bthe National Heart and Lung Institute, Royal Brompton Hospital, London; cthe Asthma & Allergy Clinic, Hochgebirgsklink, Davos Wolfgang; and dRoche Laboratories, Brussels.

    ☆☆

    Supported by Network Centre of Excellence for Respiratory Diseases and Medical Research Council, Canada.

    ★

    Reprint requests: Q. Hamid, MD, PhD, Meakins-Christie Laboratories, 3626 Rue St. Urbain, Montreal, Quebec, Canada H2X 2P2.

    ★★

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