BACKGROUND: IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors consist of cytokine-specific alpha-subunits, which associate with a shared signalling common beta-subunit (beta(c)) to form a high-affinity complex. The expression of IL-3, IL-5, and GM-CSF is upregulated in atopic inflammation, and these cytokines are thought to contribute to pathology through mechanisms that include eosinophil activation. OBJECTIVE: We sought to examine the distribution of receptor expression between cells relevant to allergic inflammation from individual subjects and to compare atopic and nonatopic individuals. METHODS: Peripheral blood was obtained from atopic and nonatopic volunteers. Cytokine-receptor expression was examined by flow cytometry with monoclonal antibodies specific for alpha-subunits and beta(c) in combination with phenotypic markers for eosinophils, basophils, neutrophils, dendritic cells, monocytes, and T cells. RESULTS: Using a ligand-independent system, we confirmed the cellular distribution of IL-5Ralpha, IL-3Ralpha, and GM-CSFRalpha. IL-3Ralpha and GM-CSFRalpha were detected on high-affinity IgE receptor blood dendritic cells. Beta(c) expression was detected on basophils, eosinophils, neutrophils, and, at low levels, on monocytes and dendritic cells. There was intense staining of basophils for IL-3Ralpha relative to IL-5Ralpha, GM-CSFRalpha, and beta(c), whereas eosinophil-staining intensity was similar for IL-3Ralpha, IL-5Ralpha, GM-CSFRalpha, and beta(c). There were no significant differences between atopic and nonatopic subjects in cytokine-receptor staining. CONCLUSION: IL-3Ralpha and GM-CSRalpha are shown on a newly defined population of Fc(epsilon)RI-high dendritic cells. The intense staining of basophils for IL-3Ralpha, relative to that of IL-5Ralpha and GM-CSFRalpha, is in contrast to eosinophils from the same subjects and may explain the higher sensitivity of basophils to IL-3 compared with IL-5 and GM-CSF. We found no evidence for downregulation of receptor expression in atopic compared with nonatopic subjects, suggesting that these receptors remain accessible as potential targets for therapeutic intervention in atopic allergic disease.
BACKGROUND:IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors consist of cytokine-specific alpha-subunits, which associate with a shared signalling common beta-subunit (beta(c)) to form a high-affinity complex. The expression of IL-3, IL-5, and GM-CSF is upregulated in atopic inflammation, and these cytokines are thought to contribute to pathology through mechanisms that include eosinophil activation. OBJECTIVE: We sought to examine the distribution of receptor expression between cells relevant to allergic inflammation from individual subjects and to compare atopic and nonatopic individuals. METHODS: Peripheral blood was obtained from atopic and nonatopic volunteers. Cytokine-receptor expression was examined by flow cytometry with monoclonal antibodies specific for alpha-subunits and beta(c) in combination with phenotypic markers for eosinophils, basophils, neutrophils, dendritic cells, monocytes, and T cells. RESULTS: Using a ligand-independent system, we confirmed the cellular distribution of IL-5Ralpha, IL-3Ralpha, and GM-CSFRalpha. IL-3Ralpha and GM-CSFRalpha were detected on high-affinity IgE receptor blood dendritic cells. Beta(c) expression was detected on basophils, eosinophils, neutrophils, and, at low levels, on monocytes and dendritic cells. There was intense staining of basophils for IL-3Ralpha relative to IL-5Ralpha, GM-CSFRalpha, and beta(c), whereas eosinophil-staining intensity was similar for IL-3Ralpha, IL-5Ralpha, GM-CSFRalpha, and beta(c). There were no significant differences between atopic and nonatopic subjects in cytokine-receptor staining. CONCLUSION:IL-3Ralpha and GM-CSRalpha are shown on a newly defined population of Fc(epsilon)RI-high dendritic cells. The intense staining of basophils for IL-3Ralpha, relative to that of IL-5Ralpha and GM-CSFRalpha, is in contrast to eosinophils from the same subjects and may explain the higher sensitivity of basophils to IL-3 compared with IL-5 and GM-CSF. We found no evidence for downregulation of receptor expression in atopic compared with nonatopic subjects, suggesting that these receptors remain accessible as potential targets for therapeutic intervention in atopic allergic disease.
Authors: Namita A Gandhi; Brandy L Bennett; Neil M H Graham; Gianluca Pirozzi; Neil Stahl; George D Yancopoulos Journal: Nat Rev Drug Discov Date: 2015-10-16 Impact factor: 84.694
Authors: K Ogawa; R Hashida; M Miyagawa; S Kagaya; Y Sugita; K Matsumoto; T Katsunuma; A Akasawa; G Tsujimoto; H Saito Journal: Clin Exp Immunol Date: 2003-03 Impact factor: 4.330
Authors: Lisa M Ganley-Leal; Pauline N Mwinzi; Catherine B Cetre-Sossah; Julius Andove; Allen W Hightower; Diana M S Karanja; Daniel G Colley; W Evan Secor Journal: Infect Immun Date: 2006-04 Impact factor: 3.441