Eopinophils as direct target of the anti-inflammatory effect of salmeterol: Demonstration with indium-111-labeled eosinophils.

ABSTRACT

The beta 2-adrenoceptor agonist salmeterol inhibits the accumulation of eosinophils at the site of allergic inflammation, but the cellular target is uncertain. This study was undertaken to determine whether eosinophils themselves are the target of this inhibitory action. Purified guinea pig peritoneal eosinophils were labeled with indium-111 oxine, pre-incubated with salmeterol or drug vehicle before being injected intravenously into guinea pigs, which have previously been immunized with ovalbumin [OA]. Four hours after intradermal injection of OA or platelet-activating factor [PAF], the accumulation of labeled eosinophils at the injection sites was determined by measuring the radioactivity in punched-out skin sites. In vitro adhesion to plastic plate was also studied by measuring the eosinophil peroxidase content of adhering cells. About 6% of the injected 111In-eosinophils were circulating 10 min after injection and remained relatively steady for over 4 h. In animals given vehicle-treated 111In-eosinophils an up to 3.6-fold increase in the accumulation of the labeled cells at the skin sites of OA or PAF injection was seen. Pretreatment of 111In-eosinophils with salmeterol [1 micro M] - a concentration giving about 65% inhibition of in vitro adherence - had no effect on the basal [PBS-induced] skin accumulation of the injected cells. However, it inhibited the net accumulation induced by OA [0.01-1 micro g/site] and PAF [0.01-1 nmol/site] by 58.8-100%. At 1 micro M, salmeterol itself had no significant effect on the viability and circulation of 111In-eosinophils. These results provide evidence for a direct inhibitory effect of salmeterol on eosinophils and suggest that this may account for a significant part of its clinical anti-inflammatory properties