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Published ahead of print on November 20, 2003, doi:10.1164/rccm.200307-1004OC

Am. J. Respir. Crit. Care Med., Volume 169, Number 5, March 2004, 573-577

A more recent version of this article appeared on March 1, 2004
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Submitted on July 23, 2003
Accepted on November 19, 2003

Sputum CD34+IL-5R{alpha}+ cells increase after allergen: evidence for in situ eosinophilopoeisis

Sandra C Dorman1, Ann Efthimiadis2, Irene Babirad2, Rick M Watson1, Judah A Denburg1, Frederick E Hargreave2, Paul M O'Byrne1, and Roma Sehmi2*

1 Medicine, McMaster University, Hamilton, Ontario, Canada, 2 St. Joseph's Hospital, Firestone Institute for Respiratory Health, Hamilton, Ontario, Canada

* To whom correspondence should be addressed. E-mail: sehmir{at}mcmaster.ca.

Eosinophil-lineage committed progenitors increase in the bone marrow of asthmatics developing allergen-induced airway hyperresponsiveness and eosinophilia. Also, higher numbers of circulating eosinophil/basophil colony forming units have been demonstrated 24h after allergen inhalation and in bronchial and nasal biopsies of allergic individuals. These cells may undergo in-situ eosinophilopoiesis, suggesting that following 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-5R{alpha}+ cells were measured in induced sputum from allergic asthmatics at baseline, 7 and 24h following 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 controls. At baseline, there were significantly fewer sputum eosinophils and CD34+ cells in normals compared to asthmatics. Sputum CD34+ cells increased at 7h following allergen inhalation in both groups of asthmatics, which was sustained at 24h in the dual responder group only, associated with sustained increases in sputum CD34+IL-5R{alpha}+ cells, eosinophils and IL-5. These results indicate that eosinophil progenitors can migrate to the airways and may differentiate towards an eosinophilic phenotype.


Key words: Stem Cell Mobilization, Asthma, Airway




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