Characterization of Macrophage Activation States in Patients With Cystic Fibrosis

J Cyst Fibros. 2010 Sep;9(5):314-22. doi: 10.1016/j.jcf.2010.04.006. Epub 2010 Jun 8.

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.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Anti-Bacterial Agents / therapeutic use
  • Arginase / metabolism
  • Azithromycin / therapeutic use
  • Biomarkers / blood
  • Cell Count
  • Child
  • Child, Preschool
  • Cystic Fibrosis / immunology*
  • Cystic Fibrosis / microbiology
  • Cystic Fibrosis / pathology
  • Cystic Fibrosis / physiopathology
  • Cytokines / metabolism
  • Female
  • Forced Expiratory Volume
  • Humans
  • Infant
  • Lectins, C-Type / metabolism
  • Macrophage Activation*
  • Macrophages / pathology
  • Male
  • Mannose-Binding Lectins / metabolism
  • Middle Aged
  • Phenotype
  • Pseudomonas Infections / complications
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / enzymology
  • Receptors, Cell Surface / metabolism
  • Steroids / therapeutic use
  • Up-Regulation
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Biomarkers
  • Cytokines
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • Steroids
  • mannose receptor
  • Azithromycin
  • Arginase