Macrophage derived chemokine (CCL22), thymus and activation-regulated chemokine (CCL17), and CCR4 in idiopathic pulmonary fibrosis.
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.
Yogo
Yurika
Y
Department of Emergency and Critical Care Medicine, School of Medicine, Keio University, Tokyo, Japan. kosajisugar08@gmail.com
Fujishima
Seitaro
S
Inoue
Takashi
T
Saito
Fumitake
F
Shiomi
Takayuki
T
Yamaguchi
Kazuhiro
K
Ishizaka
Akitoshi
A
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*
C106230:CCL17 protein, human; C515354:CCR4 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D054398:Receptors, CCR4