Cytokines directly induce degranulation and superoxide production from human eosinophils.
BACKGROUND
Cytokines are implicated in allergic diseases and can modulate effector functions of eosinophils stimulated by another agonist. However, little is known about the capacity of cytokines to directly trigger eosinophil degranulation.


OBJECTIVE
We attempted to determine whether cytokines can directly induce degranulation and superoxide production from eosinophils.


METHODS
Eosinophils from normal donors were incubated with various cytokines in albumin-coated tissue culture plates for 4 hours. To quantitate degranulation, the amounts of eosinophil-derived neurotoxin in supernatants were measured by radioimmunoassay. In addition, superoxide production was measured by superoxide dismutase-inhibitable reduction of cytochrome c.


RESULTS
IL-5, IL-3, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor- alpha, and RANTES all induced eosinophil degranulation. Granulocyte-macrophage colony-stimulating factor was the most potent and induced eosinophil-derived neurotoxin release comparable to that induced by secretory IgA beads, one of the most potent secretagogues for eosinophils. In addition, IL-5 and tumor necrosis factor- alpha were synergistic in their induction of eosinophil degranulation. In contrast, IL-1, IL-8, interferon- gamma, and macrophage inflammatory protein-1 alpha did not induce degranulation. Finally, IL-5, IL-3, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor- alpha, but not RANTES, also induced superoxide production from eosinophils.


CONCLUSIONS
Certain cytokines directly induce eosinophil degranulation and superoxide production in vitro. Therefore these cytokines may be important in the release of toxic granule proteins from eosinophils in allergic diseases.
Horie
S
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Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
Gleich
G J
GJ
Kita
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D015550:Cell Degranulation / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000494:pharmacology*; D004357:Drug Synergism; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D007700:Kinetics; D013481:Superoxides / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007377:Interleukin-3; D015848:Interleukin-5; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor