UP-REGULATION OF ALPHA-GM-CSF-RECEPTOR IN NONATOPIC ASTHMA BUT NOT INATOPIC ASTHMA

Background: Intrinsic asthma is characterized by an increased number o f activated eosinophils and macrophages and an increased expression of the hematopoietic growth factor granulocyte-macrophage colony-stimula ting factor (GMCSF) in the bronchial mucosa. Objective: This study was carried out to investigate the expression of alpha GM-CSF receptor (a lpha GM-CSBr) messenger RNA and protein in the bronchial mucosa of pat ients with intrinsic or atopic asthma and of control subjects and to c orrelate the expression of alpha GM-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 w ith 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 alpha GM-CSFr by using in situ hybridization and immunocytochemistry. Results: alpha GM-CSFr mRNA- and protein-positive cells were identified in biopsy specimens f rom ail four groups studied. There was no significant difference in th e number of cells expressing alpha GM-CSFr mRNA and protein in patient s with atopic asthma compared with atopic and nonatopic control subjec ts. However, the numbers of alpha GM-CSFr mRNA- and protein-positive c ells were significantly higher in nonatopic patients with asthma compa red with atopic patients with asthma and atopic and nonatopic control subjects (p < 0.001). In the patients with intrinsic asthma, the numbe r of alpha GM-CSFr mRNA-positive cells per millimeter of basement memb rane correlated with numbers of CD68(+) cells (r(2) = 0.87, p < 0.001) but not with EG2(+) cells, and colocalization studies demonstrated th at 80% of the cells expressing alpha GM-CSFr mRNA were CD68(+). The ex pression of GM-CSF was also significantly increased in patients with i ntrinsic asthma compared with those with atopic asthma and control sub jects (p < 0.05), In addition, in intrinsic asthma, there was a correl ation between alpha GM-CSFr mRNA and FEV1 (r(2) = 0.61, p < 0.05. Conc lusion: These results demonstrate that elevated numbers of cells expre ssing alpha GM-CSFr can be detected in nonatopic asthma but not in ato pic asthma and suggest that this increased expression is predominantly macrophage-associated and may play an important pathophysiologic role in intrinsic asthma.