Interleukin-5 in growth and differentiation of blood eosinophil progenitors in asthma: effect of glucocorticoids

Br J Pharmacol. 2001 Dec;134(7):1539-47. doi: 10.1038/sj.bjp.0704389.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD34 / immunology
  • Asthma / pathology
  • Asthma / physiopathology*
  • Cell Differentiation / drug effects*
  • Cell Division / drug effects*
  • DNA, Antisense / pharmacology
  • Dexamethasone / pharmacology
  • Eosinophils / cytology
  • Eosinophils / drug effects*
  • Eosinophils / immunology
  • Female
  • Gene Expression
  • Glucocorticoids / pharmacology
  • Humans
  • Interleukin-5 / genetics
  • Interleukin-5 / pharmacology*
  • Interleukin-5 / physiology
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Male
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Interleukin / immunology
  • Receptors, Interleukin-5
  • Stem Cells / drug effects

Substances

  • Antibodies, Monoclonal
  • Antigens, CD34
  • DNA, Antisense
  • Glucocorticoids
  • Interleukin-5
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-5
  • Dexamethasone