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1 Institut National de la Santé et de la Recherche Médicale (INSERM) U425, Neuroimmunopharmacologie Pulmonaire, Faculté de Pharmacie, Université Louis Pasteur Strasbourg I, Illkirch Cedex, and 2 Service de Pneumologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 3 Dept of Medicine, Division of Respiratory Medicine, Karolinska Hospital, Stockholm, Sweden
CORRESPONDENCE: C. Olgart Höglund, INSERM U425, Neuroimmunopharmacologie Pulmonaire, Faculté de Pharmacie, Université Louis Pasteur Strasbourg I, B.P. 24, 67 401 Illkirch Cedex, France. Fax: 33 390244309. E-mail: caroline.olgart@fyfa.ki.se
Keywords: airwayasthmainflammationnerve growth factorneurotrophin
Received: January 16, 2001
Accepted June 26, 2002
This study was founded by INSERM. C. Olgart Höglund was supported by the Swedish Research Council (Sweden), Torsten and Ragnar Söderberg's Foundation, Erik and Edith Fernström's Foundation, Comité Départemental du Bas-Rhin Contre les Maladies Respiratoires et la Tuberculose, UCB Institute of Allergy (Brussels, Belgium).
Nerve growth factor (NGF) has recently been suggested to be an important mediator of inflammation. In support of this, serum levels of NGF have been shown to be enhanced in asthmatics. However, it has not yet been shown whether the levels of NGF are also altered locally in asthmatic airways, when compared with healthy subjects, and the localisation of potential sources of NGF in the human bronchus have not yet been described. The aim of the present study was to assess NGF levels in bronchoalveolar lavage fluid (BALF) from asthmatics and to compare them to those of control subjects. Furthermore, the authors wanted to localise potential sources of NGF in bronchial tissue, and to number NGF-immunopositive infiltrating cells in the bronchial submucosa.
BALF and bronchial biopsies were obtained from seven control subjects and seven asthmatic patients by fibreoptic bronchoscopy. NGF protein levels were quantified by enzyme-linked immunosorbent assay in BALF. NGF localisation was examined by immunohistochemistry on bronchial biopsy sections.
The asthmatics exhibited significantly enhanced NGF levels in BALF. Intense NGF-immunoreactivity was observed in bronchial epithelium, smooth muscle cells and infiltrating inflammatory cells in the submucosa, and to a lesser extent in the connective tissue. The asthmatics exhibited a higher number of NGF-immunoreactive infiltrating cells in the bronchial submucosa than control subjects.
This study provides evidence that nerve growth factor is locally produced in the airways, and shows that this production is enhanced in asthmatics. These findings suggest that nerve growth factor is produced by both structural cells and infiltrating inflammatory cells in human bronchus in vivo, and the authors suggest that the increase in nerve growth factor protein in bronchoalveolar lavage fluid observed in asthmatic patients may originate both from structural cells, producing increased nerve growth factor levels in inflammatory conditons, and from the increase in nerve growth factor-immunopositive cells determined in the bronchial submucosa.
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