Hemopoietic mechanisms in nasal polyposis and asthma

In nasal polyposis and asthma, there are consistent increases in eosinophil and basophil (Eo-B) progenitors in blood and bone marrow. IL-5 plays a central role in Eo-B differentiation, exerting its effects through the IL-5 receptor expressed on Eo-B progenitors which can be found not only in blood and bone marrow but also within airway tissues such as nasal polyps and asthmatic bronchial mucosa. Little is currently known concerning regulation of IL-5Rα gene transcription in the context of commitment of hemopoietic progenitor cells to the Eo-B lineage during airway inflammation. IL-5 itself can regulate IL-5Rα expression on cord blood-derived mature (CD34^-) eosinophils and can also up-regulate IL-5Rα on bone marrow CD34⁺ eosinophil progenitors in vitro, paralleling what we have demonstrated in vivo in atopic asthmatics. Modulating agents of this IL-5Rα up-regulation include all-trans retinoic acid (ATRA), which influences granulopoiesis causing predominantly neutrophilic differentiation, while suppressing Eo-B differentiation and IL-5Rα expression; leukotriene receptor (LT1) antagonists, which act by inhibiting LTD4- and LTE4-mediated eosinophilopoiesis; and corticosteroids, which inhibit peripheral blood, but not bone marrow eosinophilopoiesis. Corticosteroids also cause increases in nasal polyp CD34⁺ progenitors, implying a block in differentiation. Thus, several anti-allergic agents differentially regulate the expression of IL-5Rα, with functional consequences in vitro and in vivo on Eo-B differentiation. The therapeutic benefit of these agents in allergic airways inflammation may be related to the degree to which Eo-B differentiation is modulated.