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Prepublished online as a Blood First Edition Paper on September 25, 2003; DOI 10.1182/blood-2003-05-1618.

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Submitted May 20, 2003
Accepted September 20, 2003

Allergen exposure-induced differences in CD34+ cell phenotype; relationship to eosinophilopoietic responses in different compartments

Svetlana Sergejeva*, Anna-Karin Johansson, Carina Malmhall, and Jan Lotvall

Department of Respiratory Medicine and Allergology, The Lung Pharmacology Group, Goteborg, Sweden

* Corresponding author; email: Svetlana.Sergejeva{at}lungall.gu.se.

We 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 OVA on 5 consecutive days. Newly produced cells were labeled with a thymidine analog. Clonogenic activity and IL-5 release from BALf CD34+ cells were evaluated using cell-culture techniques. Allergen exposure induces increase in CD135+ primitive myeloid progenitors within the CD34+ cell population, without significant changes in total number of CD34+ cells or newly produced CD34+ cells. CD34+/IL-5R{alpha}+ 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 eosinophil-lineage-committed CD34+ cells towards 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-5R{alpha}.


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