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.
Miyamasu
M
M
Department of Medicine and Physical Therapy, University of Tokyo, Japan.
Hirai
K
K
Takahashi
Y
Y
Iida
M
M
Ohtoshi
T
T
Takaishi
T
T
Morita
Y
Y
Ohta
K
K
Ito
K
K
Kasahara
T
T
D008841:Actin Cytoskeleton / Q000187:drug effects; D002630:Chemotactic Factors / Q000494:pharmacology*; D015936:Complement C5a / Q000494:pharmacology*; D003571:Cytochalasin B / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D037342:Pertussis Toxin; D010972:Platelet Activating Factor / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002630:Chemotactic Factors; D004791:Enzyme Inhibitors; D016209:Interleukin-8; D010972:Platelet Activating Factor; D010566:Virulence Factors, Bordetella; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins