Analysis of the prolongation of rat eosinophil survival induced by recombinant rat interleukin-5

Rat eosinophil survival was prolonged by recombinant rat IL-5 prepared by t he baculovirus expression system. The IL-5-induced prolongation of eosinoph il survival was dose-dependently inhibited by the protein synthesis inhibit or cycloheximide, the DNA-dependent RNA synthesis inhibitor actinomycin D, and the tyrosine kinase inhibitor herbimycin A. The MEK-1 inhibitor PD98059 inhibited IL-5-induced phosphorylation of both p44 and p42 MAP kinases, bu t the IL-5-induced prolongation of eosinophil survival was not inhibited. I n contrast, the JAK2 inhibitor AG490 inhibited the IL-5-induced prolongatio n of eosinophil survival. Treatment of eosinophils with IL-5 resulted in ph osphorylation of STAT5 but not STAT1, and the IL-5-induced phosphorylation of STAT5 was inhibited by AG490. These findings suggest that recombinant ra t IL-5 activates JAK2 tyrosine kinase, which phosphorylates STAT5, and indu ces protein syn thesis required for the prolongation of rat eosinophil surv ival. Copyright (C) 2000 S. Karger AG, Basel.