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

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 FEV 1 (percent predicted) and PC 20 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 ( r 2 = 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 FEV 1 ( r 2 = 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.)