Allergen exposure–induced differences in CD34+ cell phenotype: relationship to eosinophilopoietic responses in different compartments

Abstract

AbstractWe hypothesized that the allergen-induced increased number of airway eosinophils results from increased recruitment of eosinophils from bone marrow (BM) and local development of CD34+ cells into eosinophils. We also assumed that the phenotype of airway eosinophils depends on whether these cells have differentiated within BM or airway. C57BL/6 mice were sensitized and subsequently exposed to ovalbumin (OVA) on 5 consecutive days. Newly produced cells were labeled with a thymidine analog. Clonogenic activity and interleukin 5 (IL-5) release from bronchoalveolar lavage fluid (BALf) CD34+ cells were evaluated by using cell-culture techniques. Allergen exposure induces increase in CD135+ primitive myeloid progenitors within the BM CD34+ cell population, without significant changes in total number of CD34+ cells or newly produced CD34+ cells. CD34+/IL-5Rα+ cells in the first stage of cell differentiation were found only in BM, arguing that early commitment of CD34+ cells into the eosinophil lineage is restricted to the BM compartment. Allergen exposure induces a shift in differentiation of BM, blood, and BALf eosinophillineage–committed CD34+ cells toward mature eosinophils and recruitment of these cells via blood into airway. We further demonstrate in vitro that ability to multiply persists in BALf CD34+ cells but not CD34– cells, likely via autocrine IL-5 release and IL-5–induced up-regulation of IL-5Rα.