title: Interleukin-5 in growth and differentiation of blood eosinophil progenitors in asthma: effect of glucocorticoids.
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.
authors.affiliation: Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: H P
authors.initials: HP
authors.lastname: Kuo
authors.forename: C H
authors.initials: CH
authors.lastname: Wang
authors.forename: H C
authors.initials: HC
authors.lastname: Lin
authors.forename: K S
authors.initials: KS
authors.lastname: Hwang
authors.forename: S L
authors.initials: SL
authors.lastname: Liu
authors.forename: K F
authors.initials: KF
authors.lastname: Chung
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018952:Antigens, CD34 / Q000276:immunology; D001249:Asthma / Q000473:pathology / Q000503:physiopathology*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D016373:DNA, Antisense / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005260:Female; D015870:Gene Expression; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D015848:Interleukin-5 / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000276:immunology; D053649:Receptors, Interleukin-5; D013234:Stem Cells / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D016373:DNA, Antisense; D005938:Glucocorticoids; D015848:Interleukin-5; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D003907:Dexamethasone