Induction of eosinophil cytokine generation by chemoattractants

Recent studies have shown that eosinophils are capable of generating and releasing cytokines, illustrating a novel biologic aspect of eosinophils in regulating allergic inflammation by either autocrine or paracrine mechanisms. The effect of chemotactic agonists on eosinophil cytokine 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 platelet activating factor (PAF) did not exert any significant effects. The generation of IL-8 by chemoattractants was absolutely dependent on the presence of cytochalasin B. Pertussis toxin completely attenuated C5a- and FMLP-induced IL-8 production, indicating the involvement of pertussis toxin-sensitive G proteins in the signal transduction process. In situ hybridization showed that both C5a and FMLP promoted eosinophil IL-8 production via transcriptional gene activation. Furthermore, C5a 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 cytokines, which could be an important mechanism in the regulation of allergic inflammation.