Hemopoietic progenitors: the role of eosinophil/basophil progenitors in allergic airway inflammation.
Progenitor cells play important roles in the physiology and homeostasis of the overall hemopoietic system. The majority of hemopoietic activity takes place in the bone marrow, under the influence of resident marrow stromal cells, accessory cells, and/or their products. This constitutes the complex network of the hemopoietic inductive microenvironment, which is crucial for providing signals necessary for the maintenance of populations of progenitors at varying stages of lineage commitment. Accumulation of eosinophils and basophils in tissues is characteristic of allergic inflammation. A large body of evidence now exists which confirms that these tissue inflammatory events are coincident with relevant changes in progenitors; it has thus been hypothesized that the observed changes in mature cell numbers occur directly or indirectly as a result of differentiation of lineage-committed eosinophil/basophil, and perhaps other, progenitor cells. Differentiation and maturation of hemopoietic cells have traditionally been thought to be restricted to the bone marrow microenvironment. More recently, evidence has accumulated to suggest that some hemopoietic cells present in allergic tissue may be recruited from the bone marrow, traffic through the peripheral circulation and into tissues to participate in the ongoing inflammatory process at these distal sites. The clinical administration of monotherapy with topical corticosteroids, oral cysteinyl leukotriene antagonists and cytokine antagonists such as antibodies to interleukin-5, suggest that suppression of hemopoietic contributions to allergic inflammation may be necessary for full control of allergic inflammation and disease manifestations. In addition to progenitors being targets of therapy, they may well determine how and whether allergic inflammation is generated in early life, thus serving as biomarkers of disease.
Gauvreau
Gail M
GM
Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada. gauvreau@mcmaster.ca
Denburg
Judah A
JA