Eosinophil precursors constitute approximately 3% of BM progenitors, of which approximately two-thirds are myelocyte precursors and the remainder maturing eosinophils. Eosinophilic myelocytes are large cells with a bilobed nucleus (Fig.1). The characteristic specific granules of eosinophils contain major basic protein, eosinophil cationic protein, eosinophil peroxidase, and eosinophil-derived neurotoxin. Eosinophils also contain primary granules that contain Charcot-Leyden crystal protein. Mature eosinophils are released into the peripheral blood, where they circulate up to 18 hours before migrating to the tissues.

Fig1. NEUTROPHILIC, EOSINOPHILIC, AND BASOPHILIC GRANULOCYTES; THEIR MYELOCYTE PRECURSORS; AND MAST CELLS. Eosinophilic and basophilic granulocytes are always best viewed compared with neutrophilic granulocytes because staining can vary from laboratory to laboratory and even from case to case. When compared with a neutrophil (A), the eosinophil (B) has larger and more red/orange-colored and almost refractile granules than the pink and barely perceivable granules in the neutrophil. Mature eosinophils are also frequently bilobed, whereas neutrophils tend to have three or four lobes. The basophil (C) has dense, dark blue granules that frequently overlie the condensed and lobulated nucleus. These granules are much larger than the primary granules of promyelocytes. The myelocyte stage of maturation is when the secondary granules first appear (D–F). In the neutrophilic myelocyte (D), the secondary granules first appear in the Golgi region and have been described as resembling the sunrise over the horizon, the “dawn of neutrophilia.” The eosinophilic and basophilic myelocytes (E, F) are relatively infrequent in the bone marrow and are usually enumerated together with the mature forms. Mast cells (G) must be distinguished from basophils and basophilic myelocytes. Mast cells are larger and have numerous granules mostly in the cytoplasm. Mast cells have round nuclei, which are frequently obscured by the granules. A toluidine blue cytochemical reaction will be positive (metachromatic) in the granules of both basophils and mast cells. However, a mast cell tryptase immunostain used on a tissue section will be positive only in mast cells.

Eosinophils proliferate and mature under the influence of IL-3, IL-5, and GM-CSF. Evidence suggests that these cytokines are secreted by T cells as the stimulus to eosinophil production in many disorders associated with eosinophilia. Recent studies of idiopathic hypereosinophilic syndrome have described both activating mutations in and fusion partners of the platelet-derived growth factor receptor-α (PDGFR-α) that result in constitutive tyrosine kinase activation and eosinophil proliferation.

Transcriptional regulation of eosinophilic differentiation is mediated through PU.1, C/EBPα, and C/EBPβ. Because these same factors also induce myeloid differentiation, how the choice between myeloid and eosinophilic lineage is modulated is not fully understood. It has been proposed that levels of GATA-1 may determine whether C/EBP expression induces the eosinophilic or the myeloid maturation program. The transcription factor interferon regulatory factor-8 (IRF8) has also been implicated in associating with PU.1 and inhibiting C/ EBPα to preferentially direct monocytic and eosinophilic differentiation over neutrophilic production.

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مواضيع ذات صلة

Monocytopoiesis

Transcription Factors Regulating Myeloid Differentiation and Myeloid-Specific Gene Expression

Cytokine Regulation of Myeloid Proliferation and Differentiation

Neutrophil Granules and Their Content Proteins

Stages of Neutrophil Differentiation

T Lymphocytes, Transfer of Safety Genes, and Strategies to Improve Tumor Cell Specificity

Optimizing T-Cell Trafficking and Overcoming Tumor Immune Evasion

Allogeneic Banked Cells

Clinical Results of Chimeric Antigen Receptor T Cells in Hematologic Malignancies

Types of Cellular Immunotherapy

Adoptive Immunotherapy of Cancer

Therapeutic Manipulation of T-Cell-Mediated Immunity