Evidence for protein oedema, neutrophil influx, and enhanced collagen production in lungs of patients with systemic sclerosis.

Harrison, N K; McAnulty, Robin J.; Haslam, P L; Black, Carol M.; Laurent, Geoffrey J.

doi:10.1136/thx.45.8.606

Cited by 34 publications

(12 citation statements)

References 26 publications

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“…Consistent with the previous reports (21,22) the levels of total BAL protein were increased in patients (Table I). ELISA of BAL fluids from healthy volunteers and scleroderma patients with or without interstitial lung disease confirmed previous findings (8) of an increase of OSM in the lungs of patients with scleroderma lung disease compared with scleroderma patients with no pulmonary involvement or with healthy controls (Fig.…”

Section: Osm Is Elevated In Human Pulmonary Fibrosissupporting

confidence: 93%

Mechanisms of Oncostatin M-Induced Pulmonary Inflammation and Fibrosis

Mozaffarian

Brewer

Trueblood

et al. 2008

The Journal of Immunology

127

123

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Oncostatin M (OSM), an IL-6 family cytokine, has been implicated in a number of biological processes including the induction of inflammation and the modulation of extracellular matrix. In this study, we demonstrate that OSM is up-regulated in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and scleroderma, and investigate the pathological consequences of excess OSM in the lungs. Delivery of OSM to the lungs of mice results in a significant recruitment of inflammatory cells, as well as a dose-dependent increase in collagen deposition in the lungs, with pathological correlates to characteristic human interstitial lung disease. To better understand the relationship between OSM-induced inflammation and OSM-induced fibrosis, we used genetically modified mice and show that the fibrotic response is largely independent of B and T lymphocytes, eosinophils, and mast cells. We further explored the mechanisms of OSM-induced inflammation and fibrosis using both protein and genomic array approaches, generating a “fibrotic footprint” for OSM that shows modulation of various matrix metalloproteinases, extracellular matrix components, and cytokines previously implicated in fibrosis. In particular, although the IL-4/IL-13 and TGF-β pathways have been shown to be important and intertwined of fibrosis, we show that OSM is capable of inducing lung fibrosis independently of these pathways. The demonstration that OSM is a potent mediator of lung inflammation and extracellular matrix accumulation, combined with the up-regulation observed in patients with pulmonary fibrosis, may provide a rationale for therapeutically targeting OSM in human disease.

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Section: Osm Is Elevated In Human Pulmonary Fibrosissupporting

confidence: 93%

Mechanisms of Oncostatin M-Induced Pulmonary Inflammation and Fibrosis

Mozaffarian

Brewer

Trueblood

et al. 2008

The Journal of Immunology

127

123

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“…Thus increased numbers of neutrophils have been detected both in bronchoalveolar lavage fluid (BALF) and tissue specimens from patients with pulmonary fibrosis (24,34) as well as in animal models of the disease (20). Neutrophil elastase (NE), a serine protease released by neutrophils, has also been shown to be elevated in BALF and tissue specimens from patients with pulmonary fibrosis (25,51).…”

mentioning

confidence: 99%

Red blood cells increase secretion of matrix metalloproteinases from human lung fibroblasts in vitro

Fredriksson

Liu

Lundahl

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Although the pathogenesis of scleroderma lung disease (SLD) is not completely understood, it has been documented that profound fibrosis of the lungs is accompanied and preceded by inflammatory processes (3,4). Cellular infiltration of the lung interstitium and elevated numbers of inflammatory cells in the pulmonary alveoli are hallmarks of inflammatory reactions in the lungs (5,6) . The cellular influx is associated with the secretion of a broad range of mediators of inflammation, including cytokines, chemokines, and growth factors (2,(7)(8)(9).…”

mentioning

confidence: 99%

Elevated levels of leukotriene B₄ and leukotriene E₄ in bronchoalveolar lavage fluid from patients with scleroderma lung disease

Kowal-Bielecka¹,

Distler²,

Kowal³

et al. 2003

Arthritis & Rheumatism

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Objective. The leukotrienes are a family of arachidonic acid-derived lipid mediators with proinflammatory and profibrotic properties. The aim of this study was to analyze the role of leukotriene B 4 (LTB 4 ) and LTE 4 in the pathogenesis of scleroderma lung disease (SLD).Methods. Nineteen systemic sclerosis (SSc) patients with SLD, 11 SSc patients without SLD, and 10 healthy controls were studied. Bronchoalveolar lavage (BAL) fluid was obtained during routine bronchoscopy of the right middle lobe in all study subjects. Levels of LTB 4 and LTE 4 were measured using enzyme immunoassay kits.Results. Levels of LTB 4 and LTE 4 were significantly higher in SSc patients with SLD (251 ؎ 170 pg/ml and 479 ؎ 301 pg/ml, respectively), than those in patients without SLD (114 ؎ 86 and 159 ؎ 149 pg/ml) and those in normal controls (86 ؎ 49 and 110 ؎ 67 pg/ml). In the total group of patients with SSc, levels of both leukotrienes correlated positively with the total number of cells in the BAL fluid and correlated negatively with the forced vital capacity. After intravenous pulse therapy with cyclophosphamide in 6 patients, there was a significant reduction in the concentration of LTB 4 (from 380 ؎ 196 pg/ml to 155 ؎ 123 pg/ml) but no significant difference in the levels of LTE 4 (from 697 ؎ 325 pg/ml to 418 ؎ 140 pg/ml).Conclusion. Our findings show that LTB 4 and LTE 4 levels are elevated in SSc patients with SLD and correlate with parameters of inflammation in the lungs. These results indicate that leukotrienes may contribute to the pathogenesis of SLD and may represent a new therapeutic target.

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Evidence for protein oedema, neutrophil influx, and enhanced collagen production in lungs of patients with systemic sclerosis.

Cited by 34 publications

References 26 publications

Mechanisms of Oncostatin M-Induced Pulmonary Inflammation and Fibrosis

Mechanisms of Oncostatin M-Induced Pulmonary Inflammation and Fibrosis

Red blood cells increase secretion of matrix metalloproteinases from human lung fibroblasts in vitro

Elevated levels of leukotriene B₄ and leukotriene E₄ in bronchoalveolar lavage fluid from patients with scleroderma lung disease

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Evidence for protein oedema, neutrophil influx, and enhanced collagen production in lungs of patients with systemic sclerosis.

Cited by 34 publications

References 26 publications

Mechanisms of Oncostatin M-Induced Pulmonary Inflammation and Fibrosis

Mechanisms of Oncostatin M-Induced Pulmonary Inflammation and Fibrosis

Red blood cells increase secretion of matrix metalloproteinases from human lung fibroblasts in vitro

Elevated levels of leukotriene B4 and leukotriene E4 in bronchoalveolar lavage fluid from patients with scleroderma lung disease

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Elevated levels of leukotriene B₄ and leukotriene E₄ in bronchoalveolar lavage fluid from patients with scleroderma lung disease