Abstract
1. There are increased numbers of circulating CD34(+) progenitor cells for eosinophils in patients with atopic asthma, with a further increase following allergen exposure or spontaneous worsening of asthma. We investigated the expression of IL-5 and IL-5Ralpha receptor in circulating CD34(+) progenitor cells in allergic asthmatics and the effects of corticosteroids. 2. Using double-staining techniques, up to 50% of CD34(+) cells expressed intracellular IL-5, and by RT - PCR, there was significant expression of IL-5 mRNA. When cultured in a semi-liquid methylcellulose medium, there were more eosinophil colony-forming units grown from asthmatic non-adherent mononuclear cell depleted of T cells in the presence of the growth factors GM-CSF, SCF and IL-3, but not of IL-5. 3. An anti-IL-5Ralpha receptor antibody and an anti-sense IL-5 oligonucleotide reduced the number of eosinophil colony forming units. No IL-5 mRNA or protein expression on T cells was observed in asthmatics or normal subjects. In the presence of growth factors including IL-5, there were significantly greater colony numbers with eosinophilic lineage grown from either asthmatics or normal subjects. 4. Dexamethasone (10(-6) M) suppressed IL-5 mRNA and protein expression in CD34(+) cells, and reduced eosinophil colony-forming units in asthmatics, but not in normal subjects. Dexamethasone did not change the expression of IL-5Ralpha on CD34(+) cells. 5. We conclude that there is increased expression of IL-5 on blood CD34(+) cells of patients with asthma and that this expression may auto-regulate eosinophilic colony formation from these progenitor cells. Corticosteroids inhibit the expression of IL-5 in circulating CD34(+) progenitor cells.