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Ontogeny and Development
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Eosinophils develop in the bone marrow from multipotential, stem cell-derived CD34+ myeloid progenitor cells in response to eosinophilopoietic cytokines and growth factors (see Fig. 31-1). They are released into the circulation as mature cells.1–3 Important stimulatory cytokines and growth factors for eosinophils include interleukin (IL)-3, granulocyte macrophage colony stimulating factor (GM-CSF), and IL-5. Activated T cells likely are the principal sources of IL-3, GM-CSF, and IL-5 that induce eosinophil differentiation in bone marrow. However, depending on pathogenic stimuli, eosinophilopoietic cytokines may be released by other cell types, including mast cells, macrophages, natural killer cells, endothelial cells, epithelial cells, fibroblasts, and even eosinophils, themselves.4 IL-3 and GM-CSF are pluripotent cytokines that have effects on other hematopoietic lineages. IL-5 is the most selective eosinophil-active cytokine, but it is relatively late acting. Although it is both necessary and sufficient for eosinophil differentiation, IL-5 demonstrates maximum activity on the IL-5 receptor (IL-5R)-positive eosinophil progenitor pool that first is expanded by earlier acting pluripotent cytokines such as IL-3 and GM-CSF4; expression of the high affinity IL-5R is a prerequisite for eosinophil development. Exodus from the bone marrow also is regulated by IL-5. IL-3, GM-CSF, along with IL-5, promote survival, activation, and chemotaxis of eosinophils through binding to receptors that have a common β chain (CD131) with IL-5R, and unique α chains. See ch31etb0.1 for designations of many factors involved in eosinophil biology.
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