Evidence that the eosinophil is a cellular target for the inhibitory action of salmeterol on eosinophil recruitment in vivo.
Systemic administration of agents which elevate cyclic AMP (e.g., phosphodiesterase inhibitors, prostanoids, beta-adrenoceptor agonists) effectively modulates eosinophil recruitment in vivo. The present study was undertaken to evaluate whether the eosinophil itself is a cellular target for the inhibitory action of these drugs in vivo. We chose to use the long-acting beta 2-adrenoceptor agonist salmeterol to test this hypothesis. Eosinophils were pretreated with salmeterol (10(-6) M) before washing and testing in two salmeterol-sensitive systems, namely eosinophil aggregation and 111In-eosinophil accumulation in guinea-pig skin. Pretreatment with salmeterol inhibited by 65% and 43% eosinophil aggregation induced by platelet-activating factor (PAF) and human recombinant C5a, respectively. Similarly, 111In-eosinophil accumulation induced by PAF and zymosan-activated plasma, a source of guinea-pig des-Arg-C5a, was inhibited by 55% and 45%, respectively. In contrast, the level of circulating 111In-eosinophils at 1 h was enhanced by 35% in animals which received salmeterol-pretreated 111In-eosinophils. Our results suggest that the eosinophil itself is one of the cellular targets of the inhibitory action of systemically administered salmeterol on eosinophil recruitment in vivo.
Teixeira
M M
MM
Imperial College of Medicine at the National Heart and Lung Institute, London, UK. mauro.teixeira@ic.ac.uk
Hellewell
P G
PG
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002449:Cell Aggregation / Q000187:drug effects; D003864:Depression, Chemical; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects*; D006168:Guinea Pigs; D006801:Humans; D010972:Platelet Activating Factor / Q000494:pharmacology; D000068299:Salmeterol Xinafoate; D012867:Skin / Q000166:cytology / Q000187:drug effects; D015054:Zymosan / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D010972:Platelet Activating Factor; D000068299:Salmeterol Xinafoate; D015054:Zymosan; D000420:Albuterol