title: Differentiation stages of eosinophils characterized by hyaluronic acid binding via CD44 and responsiveness to stimuli.
abstract: To characterize interleukin (IL)-5-induced eosinophils, we examined the expression of CD44, very late antigen (VLA)-4, and the IL-5 receptor alpha chain, as well as the levels of eosinophil peroxidase and the generation of superoxide. Eosinophils were prepared from IL-5-transgenic mice, then characterized using electron microscopy to determine their responses to stimuli. Whereas CD44 densities remained almost constant, the level of VLA-4 increased in parallel with eosinophil maturation. Although a subset of IL-5-induced eosinophils with high side scatter recovered from bone marrow and rare ones found in blood recognized hyaluronic acid (HA), most did not have this property. Bone marrow eosinophils with high side scatter and lower density contained eosinophil peroxidase, not only in granules, but also in membranous structures for 30% of this population. This population developed HA-binding ability in response to IL-3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor, macrophage inflammatory protein (MIP)-2, monocyte chemotactic protein (MCP)-1, eotaxin, nerve growth factor (NGF), and opsonized zymosan (OZ). Peripheral blood eosinophils acquired HA-binding ability in response to the same stimuli, but their responses were less than those of bone marrow eosinophils with high levels of side scatter. However, splenic eosinophils did not respond to these stimuli. Although peripheral blood eosinophils did not proliferate when stimulated by IL-5, these were the only cells that released eosinophil peroxidase in response to IL-4, MIP-2, MCP-1, eotaxin, NGF, and OZ. With the exception of a subset of bone marrow eosinophils, the ability to acquire HA binding, but not the ability to generate superoxide, correlated with eosinophil peroxidase activity and major basic protein accumulation in the granules of maturing cells.
authors.affiliation: Department of Medical Biology, Kochi Medical School, Nankoku City, Kochi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Hashizume
authors.forename: S
authors.initials: S
authors.lastname: Kataoka
authors.forename: E
authors.initials: E
authors.lastname: Hamaguchi
authors.forename: N
authors.initials: N
authors.lastname: Morimoto
authors.forename: S
authors.initials: S
authors.lastname: Tsuru
authors.forename: S
authors.initials: S
authors.lastname: Katoh
authors.forename: K
authors.initials: K
authors.lastname: Miyake
authors.forename: K
authors.initials: K
authors.lastname: Matsushima
authors.forename: M
authors.initials: M
authors.lastname: Tominaga
authors.forename: T
authors.initials: T
authors.lastname: Kurashige
authors.forename: S
authors.initials: S
authors.lastname: Fujimoto
authors.forename: P W
authors.initials: PW
authors.lastname: Kincade
authors.forename: A
authors.initials: A
authors.lastname: Tominaga
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle; D002454:Cell Differentiation; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines / Q000494:pharmacology; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism*; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015848:Interleukin-5 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D020932:Nerve Growth Factor / Q000494:pharmacology; D009439:Neuraminidase / Q000494:pharmacology; D009895:Opsonin Proteins / Q000494:pharmacology; D009928:Organ Specificity; D010544:Peroxidases / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013481:Superoxides / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
chemical_list: C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D018960:Hyaluronan Receptors; D007377:Interleukin-3; D015848:Interleukin-5; D009895:Opsonin Proteins; D011994:Recombinant Proteins; D013481:Superoxides; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006820:Hyaluronic Acid; D015054:Zymosan; D020932:Nerve Growth Factor; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D009439:Neuraminidase