title: Phenotypic characterization of lung macrophages in asthmatic patients: overexpression of CCL17.
abstract: BACKGROUND
  Studies with monocyte-derived macrophages (MDMs) and animal models have suggested a role for alternatively activated (M2) macrophages in asthmatic inflammation, but in vivo evidence for this phenotype in human asthma is lacking.
  
  
  OBJECTIVE
  To characterize the phenotype of lung macrophages from asthmatic patients in relation to disease severity and treatment.
  
  
  METHODS
  M2 biomarkers were first identified by using MDMs exposed to T(H)2 cytokines and then used to phenotype sputum and bronchoalveolar lavage (BAL) macrophages from 12 healthy control subjects, 12 patients with mild asthma, and 14 patients with moderate asthma and to assess the effects of corticosteroids and phosphatidylinositol 3-kinase (PI3K) inhibitors.
  
  
  RESULTS
  Sputum macrophages from asthmatic patients expressed significantly more CCL17 mRNA but less CD163 than macrophages from healthy subjects. However, none of the other M2 biomarkers were differentially expressed in asthmatic patients, and ex vivo BAL cells spontaneously produced similar amounts of M2 cytokines/chemokines (IL-10, CCL17, and CCL22). CCL17 mRNA overexpression correlated weakly but significantly with sputum eosinophilia (P = .0252) and was also observed in macrophages from patients with moderate asthma treated with inhaled steroids, suggesting relative insensitivity to inhibition by corticosteroids. The PI3K inhibitor LY294002 inhibited basal CCL17 release from BAL cells and IL-4-stimulated release from MDMs.
  
  
  CONCLUSIONS
  This study does not support the existence in human asthma of the full M2 phenotype described to date but points to upregulation of CCL17 in both patients with mild and those with moderate asthma, providing a further source for this ligand of CCR4(+) cells that contributes to airways inflammation. CCL17 expression is corticosteroid resistant but suppressed by PI3K enzyme inhibitors.
authors.affiliation: Academic Unit of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Southampton, United Kingdom. k.staples@southampton.ac.uk
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Staples
authors.forename: Timothy S C
authors.initials: TS
authors.lastname: Hinks
authors.forename: Jon A
authors.initials: JA
authors.lastname: Ward
authors.forename: Victoria
authors.initials: V
authors.lastname: Gunn
authors.forename: Caroline
authors.initials: C
authors.lastname: Smith
authors.forename: Ratko
authors.initials: R
authors.lastname: Djukanović
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D015415:Biomarkers / Q000378:metabolism; D054414:Chemokine CCL17 / Q000235:genetics / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology; D010641:Phenotype; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013183:Sputum / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D054414:Chemokine CCL17; D002867:Chromones; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one