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

Sergejeva, Svetlana,1972Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för lungmedicin och allergologi,Institute of Internal Medicine, Dept of Respiratory Medicine/Allergology (författare)

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 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-5Ralpha(+) 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-5Ralpha.

Johansson, Anna-Karin,1974Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för lungmedicin och allergologi,Institute of Internal Medicine, Dept of Respiratory Medicine/Allergology (författare)
Malmhäll, Carina,1959Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för lungmedicin och allergologi,Institute of Internal Medicine, Dept of Respiratory Medicine/Allergology(Swepub:gu)xmalmc (författare)
Lötvall, Jan,1956Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för lungmedicin och allergologi,Institute of Internal Medicine, Dept of Respiratory Medicine/Allergology(Swepub:gu)xlotja (författare)
Göteborgs universitetInstitutionen för invärtesmedicin, Avdelningen för lungmedicin och allergologi (creator_code:org_t)

Av författaren/redakt...: Sergejeva, Svetl ...; Johansson, Anna- ...; Malmhäll, Carina ...; Lötvall, Jan, 19 ...

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