Differential Regulation of Human Eosinophil IL-3, IL-5, and GM-CSF Receptor α-Chain Expression by Cytokines: IL-3, IL-5, and GM-CSF Down-Regulate IL-5 Receptor α Expression with Loss of IL-5 Responsiveness, but Up-Regulate IL-3 Receptor α Expression

摘要: Our recent data suggested that tissue eosinophils may be relatively insensitive to anti-IL-5 treatment. We examined cross-regulation and functional consequences of modulation eosinophil cytokine receptor expression by IL-3, IL-5 GM-CSF, eotaxin. Incubation with IL-5, or GM-CSF led reduced IL-5R alpha, which was sustained for up 5 days. Eosinophils incubated IL-3 showed diminished respiratory burst mitogen-activated protein kinase phosphorylation in response further stimulation. In contrast these findings, IL-3R alpha increased whereas down-regulated but not affected IL-5. CCR3 transiently rapidly returned toward baseline. Eotaxin had no effect on GM-CSF. Up-regulation cytokines prevented a phosphoinositol 3-kinase inhibitor, this other signaling inhibitors down-regulation. These suggest dynamic differential regulation receptors the ligands. Since are thought involved development mobilization from bone marrow present at sites allergic inflammation, have responsiveness, explain disappointing therapy reducing airway eosinophilia asthma.