Activation and differentiation of eosinophils in asthma

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In the first series of experiments, we have developed and characterized an anti-eosinophil monoclonal antibody AE500 that had been raised by im = izing mice with blood eosinophils from patients with hypereosinophilic syndron-c. AE500 selectively reacted with blood eosinophils and neutrophils from patients with blood eosinophilia, but not from normal subjects. The reactivity of AE500 with eosinophils was induced in vitro by incubating the eosinophils with GM-CSF, but not with IL-3 or IL-5. These findings suggest that the anti-eosinophil monoclonal antibody AE500 recognizes a molecule that is expressed on eosinophils and neutrophils which have been activated by GM-CSF in vivo. In the second series of experiments, we examined the effects of cytokines on the differentiation of eosinophils from the progenitors in human cord blood. Mature eosinophils were obtained after a 4-week culture of cord blood mononuclear cells with IL-3 and IL-5. INF-r decreased the eosinophil differentiation by greater than 90%. IL-2 and IL-4 also decresed the eosinophil differentiation, but increased the number of T lymphocytes. These results suggest that IFN-r, IL-2 and IL-4 negatively regulate the differentiation of human eosinophils from the progenitors. Finally, we examined the effect of a neuropeptide substance P on the activation of human= eosinophils. Substance P caused superoxide generation and ECP release in a dose-dependent manner, the effect of which was mediated by the C-terminal peptide. In conclusion, our results indicate that cytokines and neuropeptides regulate the activation and differentiation of human eosinophils.