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A Critical Role for Eosinophils in Allergic Airways Remodeling
Alison A. Humbles,1*Clare M. Lloyd,2*Sarah J. McMillan,2Daniel S. Friend,3Georgina Xanthou,2Erin. E. McKenna,1Sorina Ghiran,1Norma P. Gerard,1Channing Yu,4Stuart H. Orkin,5Craig Gerard1
Features of chronic asthma include airway hyperresponsiveness,inflammatory infiltrates, and structural changes in the airways,termed remodeling. The contribution of eosinophils, cells associatedwith asthma and allergy, remains to be established. We showthat in mice with a total ablation of the eosinophil lineage,increases in airway hyperresponsiveness and mucus secretionwere similar to those observed in wild-type mice, but eosinophil-deficientmice were significantly protected from peribronchiolar collagendeposition and increases in airway smooth muscle. These datasuggest that eosinophils contribute substantially to airwayremodeling but are not obligatory for allergen-induced lungdysfunction, and support an important role for eosinophil-targetedtherapies in chronic asthma.
1 Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. 2 Leukocyte Biology Section, Division of Biomedical Sciences, Faculty of Medicine, Imperial College, London SW7 2AZ, UK. 3 Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02111, USA. 4 Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. 5 Department of Pediatric Oncology, Dana Farber Cancer Institute and Children's Hospital, Harvard Medical School and the Howard Hughes Medical Institute, Boston, MA 02115, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: alison.humbles{at}childrens.harvard.edu, c.lloyd{at}imperial.ac.uk
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[DOI: 10.1126/science.1104134] |Summary »|Full Text »|PDF »
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