title: Epithelial eotaxin-2 and eotaxin-3 expression: relation to asthma severity, luminal eosinophilia and age at onset.
abstract: BACKGROUND
  Eosinophilic inflammation is implicated in asthma. Eotaxin 1-3 regulate eosinophil trafficking into the airways along with other chemotactic factors. However, the epithelial and bronchoalveolar lavage (BAL) cell expression of these chemokines in relation to asthma severity and eosinophilic phenotypes has not been addressed.
  
  
  OBJECTIVE
  To measure the expression of the three eotaxin isoforms in bronchoscopically obtained samples and compare them with clinically relevant parameters between normal subjects and patients with asthma.
  
  
  METHODS
  Normal subjects and patients with asthma of varying severity recruited through the Severe Asthma Research Program underwent clinical assessment and bronchoscopy with airway brushing and BAL. Eotaxin 1-3 mRNA/protein were measured in epithelial and BAL cells and compared with asthma severity, control and eosinophilic inflammation.
  
  
  RESULTS
  Eotaxin-2 and eotaxin-3 mRNA and eotaxin-2 protein were increased in airway epithelial brushings from patients with asthma and were highest in cases of severe asthma (p values 0.0155, 0.0033 and 0.0006, respectively), with eotaxin-2 protein increased with age at onset. BAL cells normally expressed high levels of eotaxin-2 mRNA/protein but BAL fluid levels of eotaxin-2 were lowest in severe asthma. Epithelial eotaxin-2 and eotaxin-3 mRNA/protein was associated with sputum eosinophilia, lower forced expiratory volume in 1 s and more asthma exacerbations. Airway epithelial cell eotaxin-2 protein differed by asthma severity only in those with late onset disease, and tended to be highest in those with late onset eosinophilic asthma.
  
  
  CONCLUSIONS
  Epithelial eotaxin-2 and 3 are increased in asthma and severe asthma. Their expression may contribute to luminal migration of eosinophils, especially in later onset disease, asthma control and severity.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh Asthma Institute at UPMC/UPSOM, Pittsburgh, PA 15213, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Coleman
authors.forename: Chetan
authors.initials: C
authors.lastname: Naik
authors.forename: Fernando
authors.initials: F
authors.lastname: Holguin
authors.forename: Anuradha
authors.initials: A
authors.lastname: Ray
authors.forename: Prabir
authors.initials: P
authors.lastname: Ray
authors.forename: John B
authors.initials: JB
authors.lastname: Trudeau
authors.forename: Sally E
authors.initials: SE
authors.lastname: Wenzel
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000328:Adult; D017668:Age of Onset; D001249:Asthma / Q000378:metabolism*; D018893:Bronchoalveolar Lavage; D001999:Bronchoscopy; D054413:Chemokine CCL11 / Q000378:metabolism; D054423:Chemokine CCL24 / Q000378:metabolism*; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004802:Eosinophilia / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D060888:Real-Time Polymerase Chain Reaction; D018709:Statistics, Nonparametric
chemical_list: D000305:Adrenal Cortex Hormones; C120429:CCL26 protein, human; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D000075906:Chemokine CCL26; D019742:Chemokines, CC