Inhibition of eosinophil activation in bronchoalveolar lavage fluid from atopic asthmatics by Y-24180, an antagonist to platelet-activating factor

We examined the effects of Y-24180, a potent and long-acting antagonist to platelet-activating factor (PAF) receptor, on the expression of adhesion mo lecules in peripheral blood and bronchoalveolar lavage fluid (BALF) eosinop hils from atopic asthmatics. Y-24180 (20 mg/day) was administered to 4 atop ic asthmatics for 8 weeks. The number of eosinophils, the level of eosinoph il cationic protein (ECP), the bindings of soluble intercellular adhesion m olecule-1 (sICAM-1) and fibronectin (FN), and the expressions of CD11b (alp ha chain of Mac-1) and CD49d (alpha chain of VLA-4) on eosinophils were eva luated in peripheral blood (n=4) and BALF (n=3) before and after the admini stration of Y-24180. The infiltration of eosinophils into the bronchial wal l was also examined by taking biopsies. Eosinophil count, sICAM-1 and FN bi nding to eosinophils in BALF significantly decreased after the administrati on of Y-24180 (p<0.05). The level of CD11b expression also decreased remark ably after the administration (n=2). In peripheral blood, eosinophil count and ECP level did not change. The binding of sICAM-1 and FN, and expression of CD11b on eosinophils in peripheral blood showed a tendency to decrease after the administration. The level of CD49d expression on eosinophils chan ged neither in BALF nor in blood. Eosinophil infiltration into the bronchia l wall markedly decreased in one out of 3 cases after the administration. T hese results suggest that Y-24180 inhibits the activation of eosinophils by antagonizing the actions of PAF in atopic asthmatics.