Studies of hepatocyte growth factor in bronchoalveolar lavage fluid in chronic interstitial lung diseases.

Abstract

Previous studies have suggested that hepatocyte growth factor (HGF) inhibits lung fibrosis as an antagonist of transforming growth factor β (TGF‑β). We assessed HGF expression levels in the lower airways of patients with selected interstitial lung diseases. HGF levels were examined by an enzyme‑linked immunosorbent assay in bronchoalveolar lavage (BAL) fluid supernatants from patients with pulmonary sarcoidosis (PS, n = 52), idiopathic pulmonary fibrosis (IPF, n = 23), nonspecific interstitial pneumonia (NSIP, n = 14), extrinsic allergic alveolitis (EAA, n = 6), bronchiolitis obliterans organizing pneumonia (BOOP, n = 8), chronic eosinophilic pneumonia (EP, n = 6), and in control subjects (n = 13). Intracellular HGF expression in BAL cells was evaluated by flow cytometry. HGF concentrations were elevated in BAL fluid from nonsmokers with IPF (261 ±204 pg/ml, P <0.02), smokers with IPF (220 ±13 pg/ml, P <0.001), and smokers with PS (172 ±33 pg/ml, P <0.02), as compared with controls (148 ±17 pg/ml for nonsmokers; 137 ±9 pg/ml for smokers). HGF levels were positively correlated with TGF‑β concentrations in BAL fluid (r = 0.3; P = 0.02) and negatively-with vital capacity (r = -0.2; P = 0.02). BAL neutrophils, and, for the first time, BAL lymphocytes, were identified as intracellular HGF‑positive cells. Our results do not support evidence for strong antifibrotic HGF activity. The highest HGF concentrations were observed in BAL fluid from patients with IPF, and they were also positively correlated with TGF‑β levels. Thus, although the local protective mechanisms such as the HGF expression are upregulated in chronic interstitial lung diseases, they are not enough to prevent lung fibrosis.