Functional expression of IL-12 receptor by human eosinophils: IL-12 promotes eosinophil apoptosis.
In murine models of allergic inflammation, IL-12 has been shown to decrease tissue eosinophilia, but the underlying mechanisms are not known. We evaluated the expression of IL-12R and the effect of IL-12 on eosinophil survival. In situ hybridization demonstrated the presence of mRNA and immunoreactivity for IL-12Rbeta1 and -beta2 subunits in human peripheral blood eosinophils. Surface expression of IL-12Rbeta1 and -beta2 subunits on freshly isolated human eosinophils was optimally expressed after incubation with PMA. To determine the functional significance of IL-12R studies, we studied cell viability and apoptosis. Morphological analysis and propidium iodide staining for cell cycle demonstrated that recombinant human IL-12 increased in vitro human eosinophil apoptosis in a dose-dependent manner. Addition of IL-5 together with IL-12 abrogated eosinophil apoptosis, suggesting that IL-12 and IL-5 have antagonistic effects. Our findings provide evidence for a novel role for IL-12 in regulating eosinophil function by increasing eosinophil apoptosis.
Nutku
E
E
Meakins-Christie Laboratories, Department of Medicine, McGill University, 3626 Saint Urbain Street, Montreal, Quebec, Canada H2X 2P2.
Zhuang
Q
Q
Soussi-Gounni
A
A
Aris
F
F
Mazer
B D
BD
Hamid
Q
Q
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D002462:Cell Membrane / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000502:physiology*; D015848:Interleukin-5 / Q000494:pharmacology; D012333:RNA, Messenger / Q000097:blood; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000502:physiology; D053707:Receptors, Interleukin-12; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
C508439:IL12RB2 protein, human; D015848:Interleukin-5; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12; D013755:Tetradecanoylphorbol Acetate