M. Humbert

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 + cells ( r 2 = 0.87, p + 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 1 ( r 2 = 0.61, p 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.)

T-Cells in the Pathogenesis of Asthma and Allergic Diseases

T-cells have a central role to play in an antigen-driven inflammatory process, since they are the only cells capable of recognizing antigenic material after processing by antigen presenting cells. CD4+ and CD8+ T lymphocytes activated in this manner elaborate a wide variety of protein mediators, including cytokines, which have the capacity to orchestrate the differentiation, recruitment, accumulation, and activation of specific granulocytes at mucosal surfaces. T-cell derived products can also influence immunoglobulin production by plasma cells. There now exists considerable support for the hypothesis that allergic diseases and asthma represent specialized forms of cell-mediated immunity, in which cytokines secreted predominantly by activated T-cells but also by other leukocytes such as mast cells and eosinophils bring about the specific accumulation and activation of eosinophils. This observation has important implications for future therapeutic procedures since it suggests that drugs modulating T-lymphocyte function may be of considerable interest in allergic conditions and asthma. This chapter summarizes the possible role of T-cells in allergic diseases and possible therapeutic manipulation of inappropriate T-cell activation in humans.