Allergen exposure-induced differences in CD34+ cell phenotype: relationship to eosinophilopoietic responses in different compartments.
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-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 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-5R alpha.
D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D004804:Eosinophils / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D015848:Interleukin-5 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology
D000485:Allergens; D018952:Antigens, CD34; D000963:Antimetabolites; D015848:Interleukin-5; D010047:Ovalbumin; D001973:Bromodeoxyuridine