SELECTIVE-INHIBITION OF IL-5 RECEPTOR ALPHA-CHAIN GENE-TRANSCRIPTION BY IL-5, IL-3, AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR INHUMAN BLOOD EOSINOPHILS

High affinity receptor for IL-5 (IL-SR), a predominant eosinophil matu ration factor, is composed of an IL-5-binding or-chain (IL-5R alpha) a nd a signal-transducing beta-chain that is shared by IL-3 and granuloc yte-macrophage CSF (GM-CSF) receptors (IL-SR and GM-CSFR), By Northern blot analysis of mRNAs obtained from normal human blood eosinophils, we show in this report that the hematopoietic cytokines IL-5, IL-3, an d GM-CSF down-regulate IL-5R alpha mRNA while up-regulating alpha-chai n mRNAs for both IL-3R and GM-CSFR as well as the beta-chain mRNA, Mor e detailed characterization reveals that the down-regulation of IL-5R alpha mRNA is specific to IL-3, IL-5, and GM-CSF; occurs very rapidly (reaching maximum inhibition within 2 h); is cytokine dose dependent; and does not require protein synthesis. Nuclear run-on and mRNA stabil ity experiments demonstrate that cytokine-induced inhibition of IL-5R alpha mRNA accumulation occurs at the level of IL-5R alpha gene transc ription, whereas enhanced accumulation of mRNAs for IL-3R alpha and th e beta-chain results from reduced mRNA degradation. We suggest from th ese experiments that in human blood eosinophils, IL-5R alpha gene tran scription and IL-5R alpha mRNA metabolism can be regulated by mechanis ms that are distinct from those used for IL-3R alpha and GM-CSFR alpha .