Interferon-gamma induces interleukin-3 release from peripheral blood eosinophils.
Interferon-gamma (IFN-gamma) upregulates eosinophil effector functions and prolongs the in vitro survival of eosinophils. We examined the possible capacity of IFN-gamma to stimulate eosinophils to produce eosinophil-activating cytokines. Eosinophils purified from mild atopic volunteers were cultured with 100 U/ml IFN-gamma. Viability of eosinophils was counted and supernatants were tested for the presence of cytokines by neutralization of eosinophil viability-enhancing activity with specific antibodies to IFN-gamma, interleukin-5 (IL-5), IL-3, or granulocyte-macrophage colony-stimulating factor (GM-CSF). IFN-gamma-enhanced eosinophil viability was up to 95% on the 4th day of culture. Pretreatment with anti-IL-3 antibody partially blocked the IFN-gamma-enhanced eosinophil survival. IFN-gamma-stimulated eosinophil supernatants had eosinophil survival. IFN-gamma-stimulated eosinophil supernatants had eosinophil viability-enhancing activity that was blocked by pretreatment not only with anti-IFN-gamma but also with anti-IL-3. Antibodies to IL-5 or GM-CSF did not have the blocking effect. To further confirm the production of IL-3 by eosinophils, we performed reverse transcription polymerase chain reaction (RT-PCR) for IL-3 messenger RNA (mRNA) in IFN-gamma-stimulated eosinophils. Significant IL-3 mRNA expression in eosinophils was observed at 6 h of incubation with IFN-gamma. These results suggest that IFN-gamma stimulates the autocrine function of eosinophils and may play an important role in allergic inflammation.
Fujisawa
T
T
Mie National Hospital, Japan.
Fukuda
S
S
Atsuta
J
J
Ichimi
R
R
Kamiya
H
H
Sakurai
M
M
D002470:Cell Survival / Q000187:drug effects; D004804:Eosinophils / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood; D007371:Interferon-gamma / Q000494:pharmacology*; D007377:Interleukin-3 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
D007377:Interleukin-3; D012333:RNA, Messenger; D007371:Interferon-gamma