title: Characterization of macrophage activation states in patients with cystic fibrosis.
abstract: BACKGROUND
  Chronic airway inflammation characterizes patients with cystic fibrosis (CF). The role of alternative macrophage activation in this disease course is unknown.
  
  
  OBJECTIVE
  We evaluated markers of alternative and classical macrophage activation in the lungs of patients with CF and evaluated these characteristics in the context of Pseudomonas aeruginosa (PA) infection, immunomodulatory drug therapy and pulmonary function.
  
  
  METHODS
  Bronchoalveolar lavage or spontaneously expectorated sputum samples were collected from 48 CF patients. Clinical data were related to macrophage surface expression of mannose receptor (MR) (up-regulated in alternatively activated macrophages) and TLR4 (up-regulated in classically activated macrophages). Also, the activity of the alternatively activated macrophage effector molecule arginase was compared among patient groups, and pro- and anti-inflammatory cytokines produced by alternatively and classically activated macrophages were measured.
  
  
  RESULTS
  There were significant differences between PA-infected and -uninfected patients in several clinical measurements. PA-infected patients exhibited increased use of azithromycin, up-regulation of MR on CD11b+ cells and increased arginase activity in their lung samples, and had a strong inverse relationship between MR and arginase activity to FEV(1). Upon further analysis, PA-infected patients who were treated with azithromycin had the highest arginase activity and the highest number of macrophages that were MR+TLR4-, and both of these markers were inversely related to the FEV(1).
  
  
  CONCLUSIONS
  Our findings suggest an increase in both MR and arginase expression as pulmonary function declines in PA-infected patients with CF. These markers of an alternatively activated macrophage phenotype give cause for future study to define the function of macrophage activation states in the CF lung.
authors.affiliation: Department of Internal Medicine, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA. bsmurp1@uky.edu
authors.forename: Brian S
authors.initials: BS
authors.lastname: Murphy
authors.forename: Heather M
authors.initials: HM
authors.lastname: Bush
authors.forename: Vidya
authors.initials: V
authors.lastname: Sundareshan
authors.forename: Christina
authors.initials: C
authors.lastname: Davis
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hagadone
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Cory
authors.forename: Heather
authors.initials: H
authors.lastname: Hoy
authors.forename: Don
authors.initials: D
authors.lastname: Hayes
authors.forename: Michael I
authors.initials: MI
authors.lastname: Anstead
authors.forename: David J
authors.initials: DJ
authors.lastname: Feola
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001119:Arginase / Q000378:metabolism; D017963:Azithromycin / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007223:Infant; D037181:Lectins, C-Type / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000473:pathology; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D011552:Pseudomonas Infections / Q000150:complications / Q000188:drug therapy / Q000201:enzymology; D011956:Receptors, Cell Surface / Q000378:metabolism; D013256:Steroids / Q000627:therapeutic use; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D016207:Cytokines; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D013256:Steroids; D017963:Azithromycin; D001119:Arginase