Bone Marrow Function in Development of Childhood Asthma

摘要

Asthma is the most common reason for hospitalization of children in both military and civilian hospitals. In children with asthma, pulmonary exposure to allergen results in damage to bronchioles by invasion of eosinophils. Eosinophils are inflammatory cells, have limited life spans, and must be continually renewed from hematopoietic tissue. We have adapted an animal model of asthma for studies of the effect of pulmonary allergen exposure on eosinophil progenitor cells (CFU- eo). These studies previously revealed that CFU-eo numbers were elevated in the bone marrow of asthmatic mice following pulmonary allergen exposure. IL-5 is the primary cytokine that regulates eosinophil production and we demonstrated that fibroblastic bone marrow stromal cells produce IL-5 and that stromal cells regulate eosinophil production in vitro. However, the relative role of bone marrow stromal cells and T lymphocytes in eosinophilia that accompanies chronic asthma has not been investigated. The primary objective of this study is to determine the role of stromal cells in normal and asthmatic eosinophil production and the extent to which inflammatory mediators released in asthma affect stromal cell function. Data presented in this report document our progress to date in this investigation and present a refined working hypothesis of regulation of altered eosinophil production in onset of asthma. Better understanding of cellular and molecular mechanisms involved in initiation and progression of disease is essential for design of more effective intervention strategies to interrupt growing incidence of this disease.