du Bois, RM;
Tumour necrosis factor-alpha production in fibrosing alveolitis is macrophage subset specific.
365 - 372.
Background: Previous studies have revealed that tumour necrosis factor (TNF)-alpha is upregulated in fibrosing alveolitis (FA) in humans. The aim of this study was to compare the TNF-alpha secretory profile of alveolar macrophages (AMs) and peripheral blood monocytes (Mos) of patients with cryptogenic FA and systemic sclerosis (SSc), a rheumatological disorder in which lung fibrosis can occur. In particular, we wished to assess whether TNF-alpha levels differ between SSc patients with FA (FASSc) and a nonfibrotic group. Methods: The reverse haemolytic plaque assay was used to evaluate the secretion of cytokine at a single cell level while immunostaining allowed subtyping of AMs and Mos. Results: This study demonstrated a difference in total TNF-alpha levels produced by AMs when the levels in subjects with FA (cryptogenic FA and FASSc) were compared to levels in either SSc patients without FA (P = 0.0002) or normal healthy controls (P < 0.001). In addition, AMs from patients with FASSc secreted more TNF-<alpha> than those of patients with no FA (P = 0.003). In contrast, there were no significant differences in Mo TNF-alpha secretion between the groups. A positive correlation was found between total TNF-alpha level and number of neutrophils obtained by bronchoalveolar lavage from patients with FA (r = 0.49, P < 0.04). Finally, it was demonstrated that there was significant heterogeneity of TNF-<alpha> secretion and that a numerically significant subset of mononuclear phagocytes, RFD7, was responsible for more than 80% of TNF-alpha production. Conclusion: By demonstrating the primary cell source of TNF- alpha in FASSc, more accurately targeted, possibly localized, anti-TNF strategies might be employed with success in the future
|Title:||Tumour necrosis factor-alpha production in fibrosing alveolitis is macrophage subset specific|
|Open access status:||An open access publication|
|Additional information:||UI - 21605452 LA - eng RN - 0 (Tumor Necrosis Factor) PT - Journal Article DA - 20011213 IS - 1465-9921 SB - IM CY - England|
|Keywords:||ALPHA, ALVEOLAR MACROPHAGES, ALVEOLITIS, Am, ASSAY, Blood, BLOOD MONOCYTES, BRONCHOALVEOLAR LAVAGE, Bronchoalveolar Lavage Fluid, cell, CELLS, COMPUTED- TOMOGRAPHY, control, Correlation, cytokine, difference, DISORDER, English, FACTOR ALPHA, FACTOR-ALPHA, fibrosing alveolitis, Fibrosis, future, GENE-EXPRESSION, groups, haemolytic plaque, HEALTHY, heart, Heterogeneity, HUMANS, IDIOPATHIC PULMONARY FIBROSIS, INFILTRATIVE LUNG-DISEASE, LEVEL, localized, Lung, macrophage, macrophages, Methods, MONOCLONAL-ANTIBODIES, Monocyte, Monocytes, necrosis, NECROSIS-FACTOR-ALPHA, neutrophil, neutrophils, NUMBER, Patient, patients, peripheral, PERIPHERAL BLOOD, PERIPHERAL-BLOOD, Phagocytes, Plaque, positive, production, profile, R, Result, RHEUMATOID- ARTHRITIS, SCLEROSIS, secretion, SINGLE, ST, strategies, strategy, SUCCESS, SYSTEMIC, SYSTEMIC SCLEROSIS, SYSTEMIC-SCLEROSIS, TNF, TNF ALPHA, TNF-ALPHA, Tumour, tumour necrosis, Tumour necrosis factor, tumour necrosis factor (TNF)- alpha, Animal, biosynthesis, Blood Cells, Comparative Study, cytology, disease, IM, Immunophenotyping, LA, Leukocyte Count, Macrophages, Alveolar, metabolism, pathology, physiology, Pulmonary Fibrosis, Reference Values, Scleroderma, Systemic, Support, Non-U.S.Gov't, Tumor, tumor necrosis, Tumor Necrosis Factor, TUMOR-NECROSIS-FACTOR, Variation (Genetics)|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)|
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