title: Macrophage derived chemokine (CCL22), thymus and activation-regulated chemokine (CCL17), and CCR4 in idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis (IPF) is a chronically progressive interstitial lung disease of unknown etiology. Previously, we have demonstrated the selective upregulation of the macrophage-derived chemokine CCL22 and the thymus activation-regulated chemokine CCL17 among chemokines, in a rat model of radiation pneumonitis/pulmonary fibrosis and preliminarily observed an increase in bronchoalveolar (BAL) fluid CCL22 levels of IPF patients.
  
  
  METHODS
  We examined the expression of CCR4, a specific receptor for CCL22 and CCL17, in bronchoalveolar lavage (BAL) fluid cells, as well as the levels of CCL22 and CCL17, to elucidate their pathophysiological roles in pulmonary fibrosis. We also studied their immunohistochemical localization.
  
  
  RESULTS
  BAL fluid CCL22 and CCL17 levels were significantly higher in patients with IPF than those with collagen vascular diseases and healthy volunteers, and there was a significant correlation between the levels of CCL22 and CCL17 in patients with IPF. CCL22 levels in the BAL fluid did not correlate with the total cell numbers, alveolar lymphocytes, or macrophages in BAL fluid. However, the CCL22 levels significantly correlated with the numbers of CCR4-expressing alveolar macrophages. By immunohistochemical and immunofluorescence analysis, localization of CCL22 and CCR4 to CD68-positive alveolar macrophages as well as that of CCL17 to hyperplastic epithelial cells were shown. Clinically, CCL22 BAL fluid levels inversely correlated with DLco/VA values in IPF patients.
  
  
  CONCLUSIONS
  We speculated that locally overexpressed CCL22 may induce lung dysfunction through recruitment and activation of CCR4-positive alveolar macrophages.
authors.affiliation: Department of Emergency and Critical Care Medicine, School of Medicine, Keio University, Tokyo, Japan. kosajisugar08@gmail.com
authors.forename: Yurika
authors.initials: Y
authors.lastname: Yogo
authors.forename: Seitaro
authors.initials: S
authors.lastname: Fujishima
authors.forename: Takashi
authors.initials: T
authors.lastname: Inoue
authors.forename: Fumitake
authors.initials: F
authors.lastname: Saito
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shiomi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Ishizaka
mesh_terms: D000328:Adult; D054414:Chemokine CCL17 / Q000276:immunology*; D054422:Chemokine CCL22 / Q000276:immunology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000276:immunology* / Q000473:pathology*; D054398:Receptors, CCR4 / Q000276:immunology*
chemical_list: C106230:CCL17 protein, human; C515354:CCR4 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D054398:Receptors, CCR4