title: Chemotactic agonists induce cytokine generation in eosinophils.
abstract: Recent studies have shown that eosinophils are capable of generating and releasing cytokines, providing a novel biologic aspect of eosinophils for regulating allergic inflammation by an autocrine or paracrine mechanism. Eosinophils synthesize various cytokines; however, the physiologic stimuli that trigger eosinophils to generate cytokines have not been fully elucidated. We examined the effect of chemotactic agonists on eosinophil cytokine generation by employing the determination of IL-8 as the main parameter. Both C5a and FMLP stimulated eosinophils to release IL-8, whereas platelet-activating factor and C-C chemokines did not exert any significant effects. On a molar basis, C5a was two orders of magnitude more potent than FMLP. 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 leading to these responses. Experiments of in situ hybridization and PCR amplification revealed that both C5a and FMLP promoted eosinophil IL-8 production through transcriptional gene activation. Pyrrolidine dithiocarbamate completely abrogated chemoattractant-induced IL-8 production, indicating the involvement of NF-kappa B in the cytoplasmic/nuclear signal-transduction process. Furthermore, chemoattractant-induced cytokine production was not limited to IL-8; C5a and FMLP but not platelet-activating factor induced significant secretion of granulocyte-macrophage-CSF 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.
authors.affiliation: Department of Medicine and Physical Therapy, University of Tokyo School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Miyamasu
authors.forename: K
authors.initials: K
authors.lastname: Hirai
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.forename: M
authors.initials: M
authors.lastname: Iida
authors.forename: M
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Koshino
authors.forename: T
authors.initials: T
authors.lastname: Takaishi
authors.forename: Y
authors.initials: Y
authors.lastname: Morita
authors.forename: K
authors.initials: K
authors.lastname: Ohta
authors.forename: T
authors.initials: T
authors.lastname: Kasahara
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D002631:Chemotactic Factors, Eosinophil / Q000502:physiology*; D016207:Cytokines / Q000502:physiology; D003609:Dactinomycin / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000276:immunology; D017997:Leukotriene C4 / Q000096:biosynthesis; D008222:Lymphokines / Q000502:physiology; D019402:Macrophage Inflammatory Proteins; D008969:Molecular Sequence Data; D015846:Monokines / Q000502:physiology; D037342:Pertussis Toxin; D016133:Polymerase Chain Reaction; D011759:Pyrrolidines / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D054407:Chemokine CCL4; D018946:Chemokine CCL5; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D016209:Interleukin-8; D008222:Lymphokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011759:Pyrrolidines; D013859:Thiocarbamates; D010566:Virulence Factors, Bordetella; D003609:Dactinomycin; C020972:pyrrolidine dithiocarbamic acid; D017997:Leukotriene C4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D037342:Pertussis Toxin