ALLERGEN-INDUCED INCREASES IN IL-5 RECEPTOR ALPHA-SUBUNIT EXPRESSION ON BONE-MARROW-DERIVED CD34(- A NOVEL MARKER OF PROGENITOR-CELL COMMITMENT TOWARDS EOSINOPHILIC DIFFERENTIATION() CELLS FROM ASTHMATIC SUBJECTS )

We have proposed previously that hemopoietic myeloid progenitors contr ibute to the ongoing recruitment of proinflammatory cells, namely eosi nophils, to sites of allergen challenge in allergic diseases such as a sthma, In this study, we investigated the involvement of bone marrow-d erived progenitors in the development of allergen-induced pulmonary in flammation in mild asthmatic subjects. By flow cytometry, we enumerate d the level of expression of CD34, a hemopoietic progenitor cell marke r, on bone marrow aspirates taken before and 24 h after allergen chall enge. In addition, the coexpression of the alpha-subunits of IL-3 rece ptor (IL-3R) and IL-5 receptor (IL-5R) on CD34(+) cells was investigat ed, After allergen-challenge, although no significant change in total BM CD34(+) cell numbers was observed, a significant increase in the pr oportion of CD34(+) cells expressing IL-5R alpha, but not IL-3R alpha, was detected in the 24-h post-allergen, compared with the pre-allerge n bone marrow, This was associated with a significant blood and sputum eosinophilia and increased methacholine airway responsiveness, 24 h p ost-allergen, Using simultaneous in situ hybridization and immunocytoc hemistry, we colocalized the expression of messenger RNA for membrane- bound IL-5R alpha to CD34(+) cells, In summary, our data suggest that increased expression of IL-5R alpha on CD34(+) cells favors eosinophil opoiesis and may thus contribute to the subsequent development of bloo d and tissue eosinophilia, a hallmark of allergic inflammation.