Abstract
Introduction: Previous reports have strongly suggested that HGF inhibits lung fibrosis as an antagonist of TGFβ (transforming growth factor β).
Objectives: To assess HGF expression in the lower airways of patients with interstitial lung diseases (ILDs).
Patients and methods: HGF levels were examined by ELISA in bronchoalveolar lavage (BAL) supernatants from ILD patients with pulmonary sarcoidosis (PS), IPF, nonspecific interstitial pneumonia (NSIP), extrinsic allergic alveolitis (EAA), bronchiolitis obliterans organizing pneumonia (BOOP), chronic eosinophilic pneumonia (EP), as well as in control subjects (n=52, 23, 14, 6, 8, 6, 13, respectively). Intracellular HGF expression in BAL cells was evaluated by flow cytometry.
Results: HGF concentrations were elevated in BAL among IPF nonsmokers (261±204 pg/ml, P<0.02), in IPF smokers (220±13 pg/ml, P<0.001) and in PS smokers (172±33 pg/ml, P<0.02), as compared to the controls (148±17 pg/ml for nonsmokers, 137±9 pg/ml for smokers). HGF levels were positively correlated with BAL neutrophil percentage (r = +0.3, P = 0.0002) and with TGFβ BAL concentration (r= +0.3, P=0.02). A negative correlation was found with patients' vital capacity (r = −0.2, P=0.02). For the first time BAL lymphocytes were identified as intracellular HGF positive cells.
Conclusions: We do not support the concept on strong anti-fibrotic HGF activity, since HGF highest concentration was found in BAL among IPF patients, and it was positively related to TGFβ. Protective mechanisms, characterized by HGF expression, are up-regulated in chronic ILDs, but they are not efficient enough in fibrotic lungs.
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