Increased endothelin-1 levels of BAL fluid in patients with pulmonary sarcoidosis.
OBJECTIVE
Pulmonary fibrosis in sarcoidosis is a significant cause of morbidity and mortality. Various factors have been intensely studied to define the pathogenesis of lung fibrosis in sarcoidosis. Endothelin (ET) consists of three isoforms and is known for its potent vasoconstrictor properties. ET plays an important role in the fibroproliferative process of interstitial lung diseases.


METHODS
To investigate the role of ET in the progression of pulmonary fibrosis in sarcoidosis, ET-1 and ET-3 concentrations were measured in BAL fluid (BALF) in 22 non-smoking patients with sarcoidosis and in control subjects (n = 12). Immunoreactivity of ET-1 was also evaluated in alveolar macrophages (AMs) from sarcoidosis patients. To assess the effects of ET in BALF on fibroblast proliferation, human foetal lung fibroblasts were cultured with sarcoidosis or control BALFs in the presence or absence of the ET-receptor antagonist TAK-044.


RESULTS
ET-1 levels in sarcoidosis BALF were significantly higher than those in control, whereas ET-3 levels were not different between sarcoidosis and control. ET-1 levels were correlated with the number of AMs in BALF. ET-1-immunoreactivity was found mainly in AM of sarcoidosis BALF. Sarcoidosis BALF significantly stimulated fibroblast proliferation, compared with control BALF, and the fibroblast proliferation induced by sarcoidosis BALF was inhibited by TAK-044.


CONCLUSIONS
Increased levels of ET-1 in AM could enhance fibrogenesis in pulmonary sarcoidosis.
First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan.
Kyoko
K
Terashita
Shuichi
S
Kato
Makoto
M
Sata
Sumito
S
Inoue
Hidenori
H
Nakamura
Hitonobu
H
Tomoike
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D049109:Cell Proliferation; D018450:Disease Progression; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017565:Sarcoidosis, Pulmonary / Q000378:metabolism* / Q000473:pathology
D015415:Biomarkers; D019332:Endothelin-1