Sputum CD34+IL-5Ralpha+ cells increase after allergen: evidence for in situ eosinophilopoiesis.
Eosinophil lineage-committed progenitors increase in the bone marrow of subjects with asthma developing allergen-induced airway hyperresponsiveness and eosinophilia. Also, higher numbers of circulating eosinophil/basophil cfu have been demonstrated 24 hours after allergen inhalation and in bronchial and nasal biopsies of allergic individuals. These cells may undergo in situ eosinophilopoiesis, suggesting that after allergen inhalation, progenitor cells traffic from the bone marrow to the airways, providing an ongoing source of effector cells. To examine this possibility, CD34(+) and CD34(+)IL-5Ralpha(+) cells were measured in induced sputum from allergic subjects with asthma at baseline and at 7 and 24 hours after allergen and diluent inhalation, using flow cytometry. Isolated early responders (n = 9) were contrasted to dual responders (n = 9), who develop allergen-induced sputum and blood eosinophilia and airway hyperresponsiveness, and to normal control subjects. At baseline, there were significantly fewer sputum eosinophils and CD34(+) cells in normal control subjects compared with subjects with asthma. Sputum CD34(+) cells increased at 7 hours after allergen inhalation in both groups of subjects with asthma, which was sustained at 24 hours in the dual responder group only, associated with sustained increases in sputum CD34(+)IL-5Ralpha(+) cells, eosinophils, and interleukin-5. These results indicate that eosinophil progenitors can migrate to the airways and may differentiate toward an eosinophilic phenotype.
Dorman
Sandra C
SC
Firestone Institute of Respiratory Health, Asthma Research Group, St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
Efthimiadis
Ann
A
Babirad
Irene
I
Watson
Rick M
RM
Denburg
Judah A
JA
Hargreave
Frederick E
FE
O'Byrne
Paul M
PM
Sehmi
Roma
R
D000485:Allergens / Q000009:adverse effects / Q000276:immunology; D000704:Analysis of Variance; D018952:Antigens, CD34 / Q000032:analysis / Q000276:immunology*; D001249:Asthma / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000009:adverse effects / Q000276:immunology; D016022:Case-Control Studies; D004804:Eosinophils / Q000276:immunology*; D005434:Flow Cytometry; D005541:Forced Expiratory Volume; D006410:Hematopoiesis / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000150:complications; D015848:Interleukin-5 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000276:immunology*; D007958:Leukocyte Count; D016210:Methacholine Chloride / Q000009:adverse effects / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000209:etiology / Q000276:immunology; D012130:Respiratory Hypersensitivity; D013183:Sputum / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D013997:Time Factors
D000485:Allergens; D018952:Antigens, CD34; D016085:Bronchoconstrictor Agents; D015848:Interleukin-5; D016210:Methacholine Chloride