Inhibition of eosinophil transepithelial migration and downregulation of adhesion molecule expression on eosinophils and airway epithelial cells induced by budesonide.
In asthma, eosinophil migration through the bronchial mucosa is mediated by the expression of surface molecules on eosinophils and airway epithelial cells. To characterize the activity of budesonide on eosinophil transepithelial migration, blood eosinophils were isolated from atopic asthmatic subjects and human bronchial epithelial cells (HBECs) from surgically resected bronchi. In the presence of different concentrations of budesonide (0.1-100 nM), we tested: a) eosinophil migration induced by C5a through HBEC monolayers; b) ICAM-1 expression on HBECs, stimulated with C5a and c) LFA-1 and Mac-1 expression on eosinophils, stimulated with C5a or with ah-CD23 mabs plus GM-CSF. Eosinophils showed a remarkable chemotactic response to C5a (P<0.001), that was effectively down-regulated by the presence in the chemotactic chambers of budesonide at all the concentrations tested (P<0.05). A weaker, but still present, inhibitory activity on cell locomotion was observed when HBECs or eosinophils were preincubated with budesonide before the chemotaxis assay, which was performed in absence of the drug. Preincubation of the cells with different concentrations of budesonide was also effective in down-regulating the C5a-induced ICAM-1 expression on HBECs and the ah-CD23 and GM-CSF-induced LFA-1 and Mac-1 expression on eosinophils. Thus, budesonide-induced down-regulation of eosinophil migration through airway epithelial cells is associated with, and possibly partially dependent on inhibition of adhesion molecule expression on both cell types.
Gonzalez Rodriguez
R
R
Pulmonary Division, G, Gaslini Institute, Genoa, Italy.
Silvestri
M
M
Cordone
A
A
Salami
A
A
Rossi
G A
GA
D000293:Adolescent; D001249:Asthma / Q000517:prevention & control*; D001980:Bronchi / Q000166:cytology* / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019819:Budesonide / Q000494:pharmacology* / Q000627:therapeutic use; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male
D001993:Bronchodilator Agents; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1; D019819:Budesonide