Neurotrophin system activation in bronchoalveolar lavage fluid immune cells in pulmonary sarcoidosis.
OBJECTIVE
Pulmonary sarcoidosis is a chronic granulomatous disease characterized by macrophage and CD4+ T-cell accumulation at the site of inflammation. Analysis of the cytokine network has substantially improved knowledge on immunopathogenesis of sarcoidosis. We hypothesize that neurotrophins (NTs), nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and NT-3, besides their importance in immune system activities, participate in chronic inflammatory disorders and in repair processes.


METHODS
The expression of NTs and NT receptors was assessed in broncho alveolar lavage (BAL) macrophages, CD4 and CD8 T-cells, from 10 patients with pulmonary sarcoidosis, using molecular biology, Western blotting and immunocytochemistry.


RESULTS
Increased levels of NTs and of high affinity NT receptor (Trks) transcripts and proteins in BAL macrophages, CD4+ and CD8+ T-cells from pulmonary sarcoidosis patients were demonstrated in comparison with healthy controls. Contrarily to healthy controls, in pulmonary sarcoidosis the expression of NGF was increased in alveolar macrophages as well as NGF and BDNF in CD4+ and CD8+ T-cells. An increased expression of TrkA, TrkB and TrkC receptors was also noticeable. Furthermore, BDNF expression in alveolar macrophages and NT-3 expression in the three different BAL immune cell populations investigated were induced during sarcoidosis. A significant correlation was observed between CD4:CD8 ratio, lymphocytosis, radiological stage and CD4 and CD8 NT expression.


CONCLUSIONS
These findings suggest that NTs are exaggeratedly expressed in BAL immune cells in pulmonary sarcoidosis and may participate in the progression of disease modulating immune cell functions.
Ricci
Alberto
A
Dipartimento di Scienze Cardiovascolari e Respiratorie, U.O.C. Pneumologia Ospedale Sant'Andrea, Università "La Sapienza" Roma, Italy. alberto.ricci@uniroma1.it
Mariotta
Salvatore
S
Saltini
Cesare
C
Falasca
Carlo
C
Giovagnoli
Maria Rosaria
MR
Mannino
Francesco
F
Graziano
Paolo
P
Sciacchitano
Salvatore
S
Amenta
Francesco
F
D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes; D017931:DNA Primers; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000235:genetics*; D020933:Neurotrophin 3 / Q000235:genetics; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017565:Sarcoidosis, Pulmonary / Q000235:genetics / Q000276:immunology*
D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers; D009414:Nerve Growth Factors; D020933:Neurotrophin 3