Hemopoietic Progenitor Cells and Hemopoietic Factors: Potential Targets for Treatment of Allergic Inflammatory Diseases
R. Sehmi, A. J. Baatjes and J. A. Denburg
Affiliation: Firestone Institute of Respiratory Health, and Division of Clinical Immunology and Allergy,Asthma Research Group, Department of Medicine, HSC-3V46, McMaster University, 1200 Main St. West, Hamilton, ON L8N 3Z5, Canada.
Keywords: allergic inflammation, hemopoiesis, migration of progenitors, therapy
Eosinophilic infiltration is a cardinal feature of allergic inflammation; based upon its biological actions, the eosinophil has assumed the role as the principal inflammatory cell in asthma. In assessing the mechanisms by which eosinophils are recruited to sites of inflammation, a sizeable body of evidence exists supporting the proposal that expansion of hemopoietic compartments in the bone marrow stimulates an increased turnover and traffic of mature eosinophils to the site of allergic inflammation. In addition, recent findings point to the possible egress and traffic of primitive progenitor cells to the site of inflammation where in-situ differentiation may provide a continued supply of proinflammatory cells. In the present article, we will review the evidence for these findings, and discuss the rationale for targeting hemopoiesis and migrational pathways of hemopoietic cells in the treatment of allergic disease. In this context, we will discuss the effect of corticosteroid treatment on hemopoietic mechanisms; the effects of therapies that inhibit the actions of cysteinyl leukotrienes (CysLTs); the effects of in vivo blockade of the eosinophil-active cytokine, interleukin (IL)-5; and, the effects of antihistamines on hemopoiesis. In addition, we will address the potential role that small molecular weight chemokine receptor antagonists may play in modulating progenitor cell trafficking to tissue sites of inflammation.
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