Allergen-induced increases in IL-5 receptor alpha-subunit expression on bone marrow-derived CD34+ cells from asthmatic subjects. 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 proinflammatory 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 pulmonary inflammation in mild asthmatic subjects. By flow cytometry, we enumerated the level of expression of CD34, a hemopoietic progenitor cell marker, on bone marrow aspirates taken before and 24 h after allergen challenge. In addition, the coexpression of the ␣ -subunits of IL-3 receptor (IL-3R) and IL-5 receptor (IL-5R) on CD34 ϩ cells was investigated. After allergen-challenge, although no significant change in total BM CD34 ϩ cell numbers was observed, a significant increase in the proportion of CD34 ϩ cells expressing IL-5R ␣ , but not IL-3R ␣ , 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 responsiveness, 24 h post-allergen. Using simultaneous in situ hybridization and immunocytochemistry, we colocalized the expression of messenger RNA for membrane-bound IL-5R ␣ to CD34 ϩ cells. In summary, our data suggest that increased expression of IL-5R ␣ on CD34 ϩ cells favors eosinophilopoiesis and may thus contribute to the subsequent development of blood and tissue eosinophilia, a hallmark of allergic inflammation. ( J. Clin. Invest. 1997. 100:2466-2475.)

Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor α

“…This high frequency of IL-5R staining in mice is in contrast to that in humans, in which much smaller numbers of bone marrow cells express this epitope. Furthermore, in humans this receptor also seems to be up-regulated by allergen exposure in asthmatics developing a late asthmatic reaction (15). This is in parallel with increased number of CFUs producing eosinophils in bone marrow samples taken after allergen exposure (24).…”

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

“…Presence of this additional eosinophil-differentiation pathway is supported by reports showing that allergic subjects have increased numbers of the eosinophil-lineage-committed CD34 ϩ cells in BM 12 and AW 13 and that AW CD34 ϩ cells can complete their differentiation following ex vivo stimulation with interleukin 5 (IL-5) or allergen. 14 However, whether these cells retain their ability to multiply within AW and subsequently maturate into eosinophils in vivo is not known.…”

Dendritic cells from Chlamydia‐infected mice show altered Toll‐like receptor expression and play a crucial role in inhibition of allergic responses to ovalbumin

“…Recent studies have shown that eosinophil precursors in BM are identifiable as CD34 + /IL-5R § + cells [35]. CD34 is an O-sialylated glycoprotein, whose expression within the hemopoietic system is restricted to primitive progenitor cells of all lineages [36], while IL-5R expression is essentially limited to eosinophil and basophil lineages [37,38]. We found that most of the IL-5R § + cells in BM were CD34 + cells in our model (data not shown).…”