Interleukin-5 is a human basophilopoietin: induction of histamine content and basophilic differentiation of HL-60 cells and of peripheral blood basophil-eosinophil progenitors

Abstract

Cytokine-induced differentiation of basophils may contribute to various inflammatory processes. We examined the effects of recombinant human interleukin-5 (IL-5) and other human cytokines in vitro on myeloid colony formation in methylcellulose and on alkaline passaged HL-60 basophilic cell differentiation. Myeloid colonies (CFU-C) at day 14, formed in the presence of either IL-3, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), or G-CSF included peripheral blood- derived progenitors of the eosinophil/basophil lineage. IL-5 stimulated a greater proportion of basophil-containing, histamine-positive, eosinophil-type colonies compared with GM-CSF, IL-3, or G-CSF. IL-5 also stimulated dose-dependent increases in histamine content of alkaline-passaged, butyrate cotreated HL-60 cells. The concentration of IL-5 required for half-maximal induction of HL-60 histamine content was similar within twofold to that needed for half-maximal stimulation of the multifactor dependent TF-1 erythroleukemic cell line. Neutralizing rat monoclonal antibodies to human IL-5 were developed and used to demonstrate that each of these IL-5 bioactivities could be specifically blocked. We conclude that in addition to its previously described eosinophil differentiation activity, IL-5 may be considered a basophilopoietin.

Effect of inhaled interleukin‐5 on eosinophil progenitors in the bronchi and bone marrow of asthmatic and non‐asthmatic volunteers

“…The lack of effect of IL-5 inhalation on the number of neutrophils and macrophages is not unexpected and confirms the selectivity of IL-5. The lack of effect of IL-5 on basophils is more unexpected, given previous reports of IL-5 responsiveness of these cells [28]. However, basophils are less numerous in the airway infiltrate than eosinophils in asthma [29] and they predominantly Table 2.…”

The GM–CSF/IL‐3/IL‐5 cytokine receptor family: from ligand recognition to initiation of signaling

“…Unlike GM-CSF and IL-3, IL-5 is a cytokine that exhibits lineage restriction. It stimulates the proliferation, maturation, and functional activation of eosinophils (151)(152)(153)(154)(155)(156) and basophils (157)(158)(159). The major cellular source of IL-5 is T cells (160), although mast cells and to some extent eosinophils (160, 161) also produce IL-5.…”

Haemopoietic processes in allergic disease: eosinophil/basophil development

“…Many haemopoietic cytokines and growth factors have been shown to exert their effects via binding specific receptors on the cell surface. Cytokines such as stem cell factor (SCF) and IL-6 act very early in the haemopoietic lineage hierarchy [12], while other growth factors are largely responsible for the terminal differentiation of cells, such as IL-5 for eosinophils as well as basophils [13]. Regulation of IL-5 signalling in CD34 1 cells has been well (a) Proliferation, differentiation and migration of progenitors in the bone marrow and tissue is regulated through binding of cytokines and growth factors to specific receptors.…”