title: Differential role of neutrophils and alveolar macrophages in hepatocyte growth factor production in pulmonary fibrosis.
abstract: Neutrophils may participate in the development of lung fibrosis. Hepatocyte growth factor (HGF), a growth factor for type II pneumocytes, is produced by neutrophils. We measured the production of HGF by blood and alveolar neutrophils from patients with either idiopathic pulmonary fibrosis (n = 11) or connective tissue disease-associated pulmonary fibrosis (n = 10) and from control patients (n = 10). HGF secretion by alveolar macrophages and the expression of the HGF receptor by alveolar epithelial cells in pulmonary fibrosis were also evaluated. HGF was not detected in bronchoalveolar lavage fluid from controls. HGF concentration in the epithelial lining fluid from patients was 4-fold higher than in plasma, suggesting a local production within the alveolar space. Alveolar neutrophils secreted HGF in vitro. Basal HGF secretion by alveolar neutrophils positively correlated with HGF in the epithelial lining fluid (p = 0.05, rho = 0.582). HGF secretion by alveolar neutrophils could not be further stimulated with lipopolysaccharide, whereas HGF secretion by blood neutrophils doubled with lipopolysaccharide. Alveolar macrophages did not secrete HGF in vitro. The expression of the HGF receptor was greatly increased in the fibrotic lung, supporting the local function of HGF secreted by neutrophils. We conclude that neutrophils are a source of HGF in patients with pulmonary fibrosis.
authors.affiliation: INSERM Unit 408, Hôpital Bichat, Paris, France. bruno.crestani@bch.ap-hop-paris.fr
authors.forename: Bruno
authors.initials: B
authors.lastname: Crestani
authors.forename: Monique
authors.initials: M
authors.lastname: Dehoux
authors.forename: Gilles
authors.initials: G
authors.lastname: Hayem
authors.forename: Véronique
authors.initials: V
authors.lastname: Leçon
authors.forename: Francine
authors.initials: F
authors.lastname: Hochedez
authors.forename: Joëlle
authors.initials: J
authors.lastname: Marchal
authors.forename: Sandrine
authors.initials: S
authors.lastname: Jaffré
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Stern
authors.forename: Geneviève
authors.initials: G
authors.lastname: Durand
authors.forename: Dominique
authors.initials: D
authors.lastname: Valeyre
authors.forename: Michel
authors.initials: M
authors.lastname: Fournier
authors.forename: Michel
authors.initials: M
authors.lastname: Aubier
mesh_terms: D017228:Hepatocyte Growth Factor / Q000096:biosynthesis*; D006801:Humans; D016676:Macrophages, Alveolar / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000097:blood* / Q000473:pathology
chemical_list: D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met