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Defect of hepatocyte growth factor production by fibroblasts in human pulmonary emphysema

¹INSERM U700, Faculté de médecine Xavier Bichat, Université Paris 7, Paris; ²Service de chirurgie thoracique and ³Service de pneumologie, Hôpital Beaujon, Clichy; and ⁴Service de biochimie and ⁵Service de pneumologie, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France

Submitted 2 July 2004 ; accepted in final form 28 November 2004

Pulmonary emphysema results from an excessive degradation of lung parenchyma associated with a failure of alveolar repair. Secretion by pulmonary fibroblasts of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) is crucial to an effective epithelial repair after lung injury. We hypothesized that abnormal HGF or KGF secretion by pulmonary fibroblasts could play a role in the development of emphysema. We measured in vitro production of HGF and KGF by human fibroblasts cultured from emphysematous and normal lung samples. HGF and KGF production was quantified at basal state and after stimulation. Intracellular content of HGF was lower in emphysema (1.52 pg/µg, range of 0.15–7.40 pg/µg) than in control fibroblasts (14.16 pg/µg, range of 2.50–47.62 pg/µg; P = 0.047). HGF production by emphysema fibroblasts (19.3 pg/µg protein, range of 10.4–39.2 pg/µg) was lower than that of controls at baseline (57.5 pg/µg, range of 20.4–116 pg/µg; P = 0.019) and after stimulation with interleukin-1 or prostaglandin E₂. Neither retinoic acids (all-trans and 9-cis) nor N-acetylcysteine could reverse this abnormality. KGF production by emphysema fibroblasts (5.3 pg/µg, range of 2.2–9.3 pg/µg) was similar to that of controls at baseline (2.6 pg/µg, range of 1–6.1 pg/µg; P = 0.14) but could not be stimulated with interleukin-1. A decreased secretion of HGF by pulmonary fibroblasts could contribute to the insufficient alveolar repair in pulmonary emphysema.

pneumocytes; fibroblast growth factor-7; alveolar repair; retinoids

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