Induction by interferons of human eosinophil apoptosis and regulation by interleukin-3, granulocyte/macrophage-colony stimulating factor and interleukin-5.
The effects of recombinant human interferon alpha (rhIFN-alpha) and interferon gamma (rhIFN-gamma) were examined on the apoptosis of human cord blood derived eosinophils, obtained after 4 weeks of culture with recombinant human interleukin-3 (rhIL-3), granulocyte-macrophage-colony stimulating factor (rhGM-CSF) and interleukin-5 (rhIL-5). Eosinophil viability decreased remarkably after 1 week culture with rhIFN-alpha and rhIFN-gamma. Recombinant rhIFN-alpha also decreased the viability of co-existing monocytes/macrophages, whereas in contrast, rhIFN-gamma increased the percentage of viable monocytes/macrophages. There was no synergistic or additional effect of rhIFN-alpha and rhIFN-gamma on eosinophil viability. Apoptotic eosinophils, detected by their morphological characteristics, or by DNA nick end labeling in situ, increased remarkably after incubation with rhIFN-alpha and increased to a lesser extent with rhIFN-gamma. The numbers of eosinophil-phagocytosing macrophages increased after culture with rhIFN-alpha and also with rhIFN-gamma. In contrast, eosinophilopoietic cytokines such as rhIL-3, rhIL-5 and specially rhGM-CSF, significantly increased eosinophil viability, and partially rescued the effects of rhIFNs. They also decreased apoptotic eosinophil numbers and eosinophil-phagocytosing macrophage numbers. These results indicate that eosinophil viability, at least in vitro, can be differentially regulated by cytokines produced during the immune response.
Morita
M
M
Centre d'Immunologie et de Biologie Parasitaire, Unite INSERM U167, Institut Pasteur, Lille, France.
Lamkhioued
B
B
Soussi Gounni
A
A
Aldebert
D
D
Delaporte
E
E
Capron
A
A
Capron
M
M
D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology*; D010587:Phagocytosis; D011994:Recombinant Proteins / Q000494:pharmacology
D007377:Interleukin-3; D015848:Interleukin-5; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007372:Interferons