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*
Meakins-Christie Laboratories, Departments of Medicine and
Pediatrics, McGill University, Montreal, Canada
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-12R
1 and -2 subunits in human
peripheral blood eosinophils. Surface expression of IL-12R1 and
-2 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.
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