INDUCTION OF EOSINOPHIL CYTOKINE GENERATION BY CHEMOATTRACTANTS

Recent studies have shown that eosinophils are capable of generating a nd releasing cytokines, illustrating a novel biologic aspect of eosino phils in regulating allergic inflammation by either autocrine or parac rine mechanisms. The effect of chemotactic agonists on eosinophil cyto kine generation was examined by determination of interleukin-8 (IL-8) as a main parameter. Both complement C5a and N-formyl-methionyl-leucyl -phenylalanine (FMLP) stimulated eosinophils to release IL-8, but plat elet activating factor (PAF) did not exert any significant effects. Th e generation of IL-8 by chemoattractants was absolutely dependent on t he presence of cytochalasin B. Pertussis toxin completely attenuated C 5a- and FMLP-induced IL-8 production, indicating the involvement of pe rtussis toxin-sensitive G proteins in the signal transduction process, In situ hybridization showed that both C5a and FMLP promoted eosinoph il IL-8 production via transcriptional gene activation, Furthermore, C 5a and FMLP, but not PAF, induced significant secretion of granulocyte -macrophage colony-stimulating factor from eosinophils. These results indicate that C5a and FMLP stimulate eosinophils to elaborate cytokine s, which could be an important mechanism in the regulation of allergic inflammation.