Increased levels of nerve growth factor in the airways of patients with sarcoidosis

Dagnell, Charlotta; Grünewald, Johan; Idali, Farah; Wikén, Maria; Kemi, Cecilia; Sköld, C. Magnus; Planck, A.; Newman, Lee S.; Eklúnd, Anders; Höglund, Caroline Olgart

doi:10.1111/j.1365-2796.2008.01988.x

Cited by 10 publications

(11 citation statements)

References 31 publications

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“…In addition, higher NT-3 levels were associated with more advanced disease stage (Figure 1C). In line with our previous report [4], NGF was significantly elevated in sarcoidosis patients (14.8; 6.1-22.6 pg/ml) as compared to healthy subjects (4.7; 2.0-17.0 pg/ml) (p < 0.01). In the present material, NGF showed no significant association with Löfgren's syndrome or disease stage.…”

Section: Resultssupporting

confidence: 92%

“…This study also describes, for the first time, neurotrophin and neurotrophin receptor expression localization in sarcoid granulomas within the lungs and lymph nodes of patients with pulmonary sarcoidosis. We have previously reported elevation of NGF in BALF of sarcoidosis patients [4], and this study confirms those results, and extends them by including the analysis of the neurotrophins NT-3 and BDNF in both BALF and serum, and by identifying cellular sources of, and targets for, NGF, BDNF and NT-3 in the lungs of sarcoidosis patients.…”

Section: Discussionsupporting

confidence: 88%

“…BDNF concentration in serum was 16; 12-24 ng/ml. NGF levels in serum were not determined as the levels have previously been reported by us to be below detection limit [4]. …”

Section: Resultsmentioning

confidence: 99%

“…We have recently reported higher levels of nerve growth factor (NGF) in the airways of patients with sarcoidosis as compared to healthy subjects [4]. NGF, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) belong to the family of neurotrophins, and are structurally and functionally related mediators.…”

Section: Introductionmentioning

confidence: 99%

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Neurotrophins and neurotrophin receptors in pulmonary sarcoidosis - granulomas as a source of expression

et al. 2010

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BackgroundPulmonary sarcoidosis is an inflammatory disease, characterized by an accumulation of CD4+ lymphocytes and the formation of non-caseating epithelioid cell granulomas in the lungs. The disease either resolves spontaneously or develops into a chronic disease with fibrosis. The neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) have been suggested to be important mediators of inflammation and mediate tissue remodelling. In support of this, we have recently reported enhanced NGF levels in the airways of patients with pulmonary sarcoidosis. However, less is known about levels of BDNF and NT-3, and moreover, knowledge in the cellular sources of neurotrophins and the distribution of the corresponding neurotrophin receptors in airway tissue in sarcoidosis is lacking.MethodsThe concentrations of NGF, BDNF and NT-3 in bronchoalveolar lavage fluid (BALF) of 41 patients with newly diagnosed pulmonary sarcoidosis and 27 healthy controls were determined with ELISA. The localization of neurotrophins and neurotrophin receptors were examined by immunohistochemistry on transbronchial lung biopsies from sarcoidosis patients.ResultsThe sarcoidosis patients showed significantly enhanced NT-3 and NGF levels in BALF, whereas BDNF was undetectable in both patients and controls. NT-3 levels in BALF were found higher in patients with non-Löfgren sarcoidosis as compared to patients with Löfgren's syndrome, and in more advanced disease stage. Epithelioid cells and multinucleated giant cells within the sarcoid granulomas showed marked immunoreactivity for NGF, BDNF and NT-3. Also, immunoreactivity for the neurotrophin receptor TrkA, TrkB and TrkC, was found within the granulomas. In addition, alveolar macrophages showed positive immunoreactivity for NGF, BDNF and NT-3 as well as for TrkA, TrkB and TrkC.ConclusionsThis study provides evidence of enhanced neurotrophin levels locally within the airways of patients with sarcoidosis. Findings suggest that sarcoid granuloma cells and alveolar macrophages are possible cellular sources of, as well as targets for, neurotrophins in the airways of these patients.

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Section: Resultssupporting

confidence: 92%

Section: Discussionsupporting

confidence: 88%

“…BDNF concentration in serum was 16; 12-24 ng/ml. NGF levels in serum were not determined as the levels have previously been reported by us to be below detection limit [4]. …”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neurotrophins and neurotrophin receptors in pulmonary sarcoidosis - granulomas as a source of expression

et al. 2010

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“…Interest in the NTs system has grown particularly in regards to several lung diseases (23)(24)(25)(26). Under normal conditions, Trk B (the physiological high-affinity receptor for BDNF) has been found to be involved in the development and maintenance of the normal structure of the lung (27,28).…”

Section: Introductionmentioning

confidence: 99%

Diagnostic value of neurotrophin expression in malignant pleural effusions

Duysinx

Paulus

Heinen

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Neurotrophins (NTs) modulate the growth of human malignancies, including lung cancers. Our prospective study evaluated the accuracy of pleural NTs [nerve growth factor, brain-derived neurotrophic factor (BDNF), neurotrophin 3 (nT3) and 4 (nT4)] levels for differentiating benign from malignant pleural exudates. Levels of NTs were measured by ELISA in 170 patients with non-neutrophilic (<50%) exudative benign or malignant pleurisies diagnosed by pleuroscopy. Fifty-nine benign (9 infections and 50 inflammatory diseases) and 111 malignant (50 extrathoracic tumors, 51 lung cancers and 10 mesotheliomas) pleural exudates were diagnosed by thoracoscopy. Levels of BDNF were significantly higher in malignant than in benign effusions [17 pg/ml (0-367) vs. 8 pg/ml (0-51), p<0.05]. ROC analysis showed an area under the curve of 0.609 (p=0.012; best threshold 44 pg/ml). Pleural BDNF levels were significantly higher in pleural metastasis of pulmonary tumors and in mesothelioma than in pleural benign effusions. Finally, a higher proportion of pleural nT3 was detected in squamous cell lung carcinoma in comparison to that in nonsquamous cell lung carcinoma (72.7 vs. 10%, p<0.0001). NTs and particularly BDNF may play a role in the pathogenesis of malignant pleural effusions.

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Morphological and immunohistochemical comparison of intrapancreatic nerves between chronic pancreatitis and type 1 autoimmune pancreatitis

et al. 2017

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Increased levels of nerve growth factor in the airways of patients with sarcoidosis

Cited by 10 publications

References 31 publications

Neurotrophins and neurotrophin receptors in pulmonary sarcoidosis - granulomas as a source of expression

Neurotrophins and neurotrophin receptors in pulmonary sarcoidosis - granulomas as a source of expression

Diagnostic value of neurotrophin expression in malignant pleural effusions

Morphological and immunohistochemical comparison of intrapancreatic nerves between chronic pancreatitis and type 1 autoimmune pancreatitis

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