Abstract • 84

In allergic asthma, airway eosinophilia is the result of increased blood eosinophil (Eos) migration across the vascular endothelium. This process is at least partially dependent on adhesion molecule expression on Eos surface. Since treatment of asthmatic patients with inhaled corticosteroids results in a marked decrease in airway eosinophilia, the aim of the study was to evaluate in vitro the activity of budesonide (BUD) on Eos locomotion. Blood Eos, partially purified by percoll gradient from 10 asthmatics, were preincubated with BUD (from 10-10 M to 10-7 M) or with medium alone. After 8 hr incubation, we evaluated the activity of the drug on: a) LFA-1 adhesion molecule expression induced by ah-CD23 (IgE low-affinity receptor, 5 mg/ml) and GM-CSF (3 ng/ml), and b) Eos migration towards C5a (0.1 mg/ml) through human umbilical vein endothelial cell (HUVEC) monolayers. In cell cultures with medium alone, LFA-1 expression on blood Eos, measured by flow cytometry, was significantly upregulated by stimulation with ah-CD23 and GM-CSF (p<0.05). Similarly, in cell cultures with medium alone, C5a significantly enhanced blood Eos locomotion through HUVEC monolayers, evaluated by Boyden chamber assay (p<0.001). Preincubation of blood Eos with BUD was effective in downregulating Eos stimulation: indeed LFA-1 expression was inhibited by BUD 10-8 M and 10-7 M, while Eos locomotion by BUD 10-9 M, 10-8 M and 10-7 M (p<0.05, each comparison). Thus the antiinflammatory activity of BUD includes a specific inhibition of integrin expression on Eos surface and of Eos chemotaxis.

This abstract was funded by Astra Farmaceutici, Milano, Italy.