Regulatory mechanism of eosinophil peroxidase release from guinea pig eosinophils

Abstract

The regulatory mechanism of degranulation of guinea pig peritoneal eosinophils was studied by determination of eosinophil peroxidase (EPO) release. Beta-agonists, such as isoproterenol, salbutamol and fenoterol, effectively inhibited A23187-induced EPO release from guinea pig eosinophils. The inhibitory effects of beta-agonists were attenuated by pretreatment with either propranolol, a non-selective beta-antagonist, or ICI 118,551, a selective beta2-antagonist. Both theophylline and dibutyryl-cAMP (db-cAMP) also significantly inhibited A23187-induced EPO release. The inhibition of EPO release induced by db-cAMP was attenuated by pretreatment with KT5720, a protein kinase A inhibitor. In addition, calphostin C as well as cytochalasin D effectively inhibited A23187-induced EPO release. From the results of the present study, it was concluded that an increase in intracellular Ca2+ concentration may lead to exocytosis of eosinophil granules through activation of protein kinase C and microfilaments. Beta-agonists and theophylline were effective in inhibiting degranulation of eosinophils by increasing intracellular cAMP level coupled with the activation of protein kinase A.