A Novel Marker of Progenitor Cell Commitment towards Eosinophilic Differentiation

Abstract

We have proposed previously that hemopoietic myeloid progenitors contribute to the ongoing recruitment of proin- flammatory cells, namely eosinophils, to sites of allergen challenge in allergic diseases such as asthma. In this study, we investigated the involvement of bone marrow-derived progenitors in the development of allergen-induced pulmo- nary inflammation in mild asthmatic subjects. By flow cy- tometry, we enumerated the level of expression of CD34, a hemopoietic progenitor cell marker, on bone marrow aspi- rates taken before and 24 h after allergen challenge. In ad- dition, the coexpression of the a -subunits of IL-3 receptor (IL-3R) and IL-5 receptor (IL-5R) on CD34 1 cells was in- vestigated. After allergen-challenge, although no significant change in total BM CD34 1 cell numbers was observed, a significant increase in the proportion of CD34 1 cells ex- pressing IL-5R a , but not IL-3R a , was detected in the 24-h post-allergen, compared with the pre-allergen bone marrow. This was associated with a significant blood and sputum eosinophilia and increased methacholine airway responsive- ness, 24 h post-allergen. Using simultaneous in situ hybrid- ization and immunocytochemistry, we colocalized the ex- pression of messenger RNA for membrane-bound IL-5R a to CD34 1 cells. In summary, our data suggest that increased expression of IL-5R a on CD34 1 cells favors eosinophilo- poiesis and may thus contribute to the subsequent develop- ment of blood and tissue eosinophilia, a hallmark of allergic inflammation. ( J. Clin. Invest. 1997. 100:2466-2475.) Key words: CD34 • IL-5 receptorhemopoiesisasthma