HEPATOCYTE GROWTH-FACTOR IN BRONCHOALVEOLAR LAVAGE FLUIDS AND CELLS IN PATIENTS WITH INFLAMMATORY CHEST DISEASES OF THE LOWER RESPIRATORY-TRACT - DETECTION BY RIA AND IN-SITU HYBRIDIZATION

Pulmonary fibrosis is a chronic inflammatory disorder characterized by diffuse fibrous remodeling of alveolar spaces. Although much interest is focused on mechanisms of the inflammatory process in pulmonary fib rosis, little is known about the repair and regenerative process. Hepa tocyte growth factor (HGF), originally discovered as a mitogen for hep atocyte regeneration, is now recognized as a multifunctional mesenchym al factor for epithelial regeneration, including the regeneration of a lveolar type II epithelial cells. Involvement of HGF and its receptor (c-met) is evident in animal models of acute lung injury produced by h ydrochloride inhalation. We studied the role of HGF in patients with i diopathic pulmonary fibrosis (IPF) (25 cases), lung fibrosis associate d with rheumatoid arthritis (22 cases), and sarcoidosis (39 cases). Im munohistochemical evaluation demonstrated that hyperplastic alveolar t ype II epithelial cells, as well as alveolar macrophages, were strongl y stained with anti-HGF antibody in tissues of patients with IPF. The concentration of HGF in bronchoalveolar lavage fluid (BALF) was signif icantly higher than in normal controls (0.23 +/- 0.09 pg/mu g) in pati ents with IPF (0.77 +/- 0.88 pg of HGF/mu g of albumin, P < 0.001), lu ng fibrosis associated with rheumatoid arthritis (0.50 +/- 0.64 pg/mu g, P < 0.01), and sarcoidosis (0.41 +/- 0.61 pg/mu g, P < 0.05). In si tu hybridization revealed mRNA for HGF in alveolar macrophages (especi ally small monocytelike macrophages). These results indicate that the increase in HGF concentration in patients' peripheral air spaces is du e to augmented HGF production by alveolar epithelial cells and alveola r macrophages. HGF, through a paracrine mechanism, may play an importa nt role in the repair and healing of the inflammatory lung damage in p ulmonary fibrosis.