title: IL-33 promotes eosinophilia in vivo and antagonizes IL-5-dependent eosinophil hematopoiesis ex vivo.
abstract: IL-33 is an IL-1 family cytokine that elicits IL-5-dependent eosinophilia in vivo. We show here that IL-33 promotes minimal eosinophil hematopoiesis via direct interactions with mouse bone marrow progenitors ex vivo and that it antagonizes eosinophil hematopoiesis promoted by IL-5 on SCF and Flt3L primed bone marrow progenitor cells in culture. SCF and Flt3L primed progenitors respond to IL-33 by acquiring an adherent, macrophage-like phenotype, and by releasing macrophage-associated cytokines into the culture medium. IL-33-mediated antagonism of IL-5 was reproduced in part by the addition of GM-CSF and was inhibited by the actions of neutralizing anti-GM-CSF antibody. These findings suggest that the direct actions of IL-33 on bone marrow progenitors primed with SCF and Flt3L are antagonistic to the actions of IL-5 and are mediated in part by GM-CSF.
authors.affiliation: Inflammation Immunobiology Section of the Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1883, USA. kdyer@niaid.nih.gov
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Dyer
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Percopo
authors.forename: Helene F
authors.initials: HF
authors.lastname: Rosenberg
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004802:Eosinophilia / Q000139:chemically induced; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D000067596:Interleukin-33; D015848:Interleukin-5 / Q000008:administration & dosage / Q000494:pharmacology*; D007378:Interleukins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D051379:Mice; D038042:Myelopoiesis / Q000187:drug effects* / Q000502:physiology
chemical_list: D016207:Cytokines; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D015848:Interleukin-5; D007378:Interleukins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor