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.
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 alpha-subunits of IL-3 receptor (IL-3R) and IL-5 receptor (IL-5R) on CD34+ cells was investigated. After allergen-challenge, although no significant change in total BM CD34+ cell numbers was observed, a significant increase in the proportion of CD34+ cells expressing IL-5R alpha, but not IL-3R alpha, 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 alpha to CD34+ cells. In summary, our data suggest that increased expression of IL-5R alpha on CD34+ cells favors eosinophilopoiesis and may thus contribute to the subsequent development of blood and tissue eosinophilia, a hallmark of allergic inflammation.
Sehmi
R
R
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Wood
L J
LJ
Watson
R
R
Foley
R
R
Hamid
Q
Q
O'Byrne
P M
PM
Denburg
J A
JA
D000328:Adult; D000485:Allergens; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis*; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001854:Bone Marrow Cells / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation; D004391:Dust; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000473:pathology; D006801:Humans; D006968:Hypersensitivity, Delayed; D006969:Hypersensitivity, Immediate; D046911:Macromolecular Substances; D008297:Male; D008925:Mites; D006109:Poaceae / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000737:chemistry; D053649:Receptors, Interleukin-5; D014158:Transcription, Genetic
D000485:Allergens; D015703:Antigens, CD; D018952:Antigens, CD34; D004391:Dust; D046911:Macromolecular Substances; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5