Hematopoiesis

Eosinophil development is predominantly in the bone marrow, but may be found at other sites (e.g. liver or lymphoid tissue) in certain human diseases, and in other mammalian species, particularly in embryos and neonates. The formation of cytoplasmic granules begins in the late myeloblast stage and continues through the myelocyte stage. Segmentation of the nucleus begins with indentation at the myelocyte stage and is complete in the mature bone marrow eosinophil.

Eosinophil development does not take place in experimental animals deprived of T cells, and it is reduced severely in patients with T cell deficiencies, such as in AIDS. The critical T cell function is the production of the hematopoietic growth factors II.-3, GM-CSF and IL-5. These hematopoietins stimulate the growth and differentiation of distinct eosinophil precursor populations in respective order from most primitive to most differentiated, and it is thought that eosinophil development requires the sequential action of all three factors. IL-5, the eosinophil lineage-specific growth factor, is absolutely required for eosinophil development, and it has been detected in high concentrations in plasma of patients with eosinophilia.

The receptors for IL-3, GM-CSF and IL-5 are het-erodimeric, with an a chain that confers Iigand specificity and a common 3 chain that is involved in signal transduction. It is known that occupancy of the IL-5 receptor leads to activation of JAK2 kinase, MAP kinase and STAT5. Thus, these three signal transduction molecules may drive commitment to the eosinophil lineage.

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