Increased Number of Alveolar Macrophages Expressing Surface Molecules of the CD11/CD18 Family in Sarcoidosis and Idiopathic Pulmonary Fibrosis Is Related to the Production of Superoxide Anions by These Cells

Schaberg, T.; Rau, Margot; Stephan, Holger; Lode, H.

doi:10.1164/ajrccm/147.6_pt_1.1507

Cited by 45 publications

(35 citation statements)

References 38 publications

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“…Several investigators have demonstrated that alveolar macrophages isolated from the BAL of sarcoidosis patients possess an enhanced capacity to metabolize oxygen and to produce hydrogen peroxide and superoxide anions, especially under the influence of activating substances [6,[13][14][15][16]. In accordance to these in vitro observed phenomena, the EBC of sarcoidosis patients has elevated levels of 8-isoprostane [8,9], whereas in the present study a systemic redox imbalance was also observed.…”

Section: Discussionsupporting

confidence: 85%

Systemic oxidative stress in patients with pulmonary sarcoidosis

Koutsokera

Papaioannou

Malli

et al. 2009

Pulmonary Pharmacology & Therapeutics

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Background: A local redox imbalance has been reported in pulmonary sarcoidosis.However, so far no study has described a systemic redox imbalance in this context.The aim of the present study was to evaluate the systemic oxidative stress in patients with sarcoidosis and determine its relationship to treatment and indices of disease severity.Methods: 35 patients with histologically proven pulmonary sarcoidosis and 13 healthy volunteers were included in the study. All patients were studied during a stable phase of their disease. Systemic oxidative stress was quantified in serum with the use of a commercially available spectrophotometric method (D-ROM test) which determines overall oxidative stress, by measuring total hydroperoxides. Oxidative stress was expressed in conventional units, i.e. Carratelli Units (UCarr), where 1UCarr corresponds to 0.8mg/L H 2 O 2 .Results: Serum oxidative stress levels were significantly higher in patients with sarcoidosis compared to those of normal subjects (390±25 vs 300±18) UCarr respectively, p=0.04). Patients not receiving systemic corticosteroids had higher levels of oxidative stress compared to steroid-treated patients (461.5±38 vs 315±20, p<0.01) and compared to controls (461.5±38 vs 300±18 UCarr, p<0.01). Oxidative stress did not correlate with diffusion lung capacity (DLCO), partial arterial oxygen tension (PaO 2 ), MRC dyspnoea scale or chest X-ray stage. Conclusions:Systemic oxidative stress is increased in patients with stable pulmonary sarcoidosis who do not receive systemic corticosteroids. This finding suggests a sustained oxidative burden even when clinical, functional and radiological criteria indicate disease stability.

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Section: Discussionsupporting

confidence: 85%

Systemic oxidative stress in patients with pulmonary sarcoidosis

Koutsokera

Papaioannou

Malli

et al. 2009

Pulmonary Pharmacology & Therapeutics

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“…The fractions of the washing-procedures were pooled and the number of cells removed was counted (MD-Kova Raster 10, Madaus, Köln, FRG). This method allows the generation of BA-cell monolayers consisting mainly of alveolar macrophages [26,27]. In our experiments, macrophage enrichment was >95%.…”

Section: Gsh-oxidation Assay Preparation Of Bronchoalveolar Inflammatmentioning

confidence: 75%

“…BA-cells obtained by BAL were cultured in a standard medium (RPMI 1640, Sigma) using 6-well, flatbottomed, plastic culture dishes (Falcon, NJ, USA) as described previously [10,[24][25][26][27]. After incubation for 30 min at 37°C with 5% CO 2 , non adherent cells were removed by washing five times with Hank's balanced salt solution (HBSS) at 37°C.…”

Section: Gsh-oxidation Assay Preparation Of Bronchoalveolar Inflammatmentioning

confidence: 99%

Increased oxidation of extracellular glutathione by bronchoalveolar inflammatory cells in diffuse fibrosing alveolitis

Behr¹,

Degenkolb²,

Maier³

et al. 1995

Eur Respir J

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An unbalanced oxidative stress is thought to be an important element in the pathogenesis of diffuse fibrosing alveolitis (DFA). The purpose of our study was to investigate the role of reactive oxygen metabolites (ROMs) released from cultured bronchoalveolar inflammatory cells (BA-cells) on glutathione oxidation. We studied bronchoalveolar lavage samples from 10 healthy controls and from 20 patients with diffuse fibrosing alveolitis (all were nonsmokers). BA-cells obtained by bronchoalveolar lavage (BAL) were incubated with 50 microM of reduced glutathione (GSH). Oxidation of GSH to glutathione disulphide (GSSG) by BA-cell derived oxidants was detected as a decline of GSH in the supernatants. Total glutathione (GSHtot = GSH + 2 GSSG) and GSSG in the epithelial lining fluid (ELF), and methionine sulphoxide (Met(O)) content of BAL proteins were determined. In diffuse fibrosing alveolitis the oxidative activity of BA-cells was enhanced, GSHtot and GSH were decreased, whereas the GSSG:GSH ratio was increased. The oxidative activity of BA-cells correlated positively with the GSSG:GSH ratio, but not with the methionine sulphoxide content. The methionine sulphoxide content was elevated in diffuse fibrosing alveolitis and inversely correlated with GSHtot. The methionine sulphoxide content also correlated positively with the percentage of BAL neutrophils. We conclude that BA-cell-derived reactive oxygen species are capable of oxidizing extracellular GSH in vitro. The positive correlation between the BA-cell oxidative activity in vitro and GSSG:GSH ratio in ELF suggests that a similar oxidative effect on extracellular GSH may also occur in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…The relative contributions of alveolar macrophages, monocytes and polymorphonuclear neutrophils to the overall respiratory burst in lung inflammatory disorders probably varies for each specific disease [4], as indicated in studies in patients with adult respiratory distress syndrome, sarcoidosis and idiopathic pulmonary fibrosis [5,6,32,37,39] as well as in animal studies, using experimental models of lung injury [40,41]. In conclusion, the present study clearly demonstrates that alveolar macrophages, monocytes and polymorphonuclear neutrophils posess significant differences in potential to increase their intracellular levels of oxidants upon stimulation.…”

Section: Discussionmentioning

confidence: 99%

Production of oxidants in alveolar macrophages and blood leukocytes

Haugen¹,

Skjonsberg²,

Kähler³

et al. 1999

Eur Respir J

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Increased production of oxidants subsequent to phagocyte stimulation has been associated with tissue damage in lung inflammatory disorders. The overall oxidative burden of the lung may vary with inflammatory cell composition.Flow cytometry using three different dyes, dihydroethidium (DHE), dichlorofluorescein diacetate (DCFH-DA) and dihydrorhodamine 123 (DHR), all compounds that by interaction with oxidants are transformed to fluorescent products, was used to examine the production of intracellular oxidants in alveolar macrophages (AMs), including size-defined subpopulations, monocytes (Ms) and polymorphonuclear neutrophils (PMNs) during in vitro incubation in the presence or absence of phorbol myristate acetate (PMA).PMA stimulation led to slightly increased (two-fold) (p<0.05) DHE-induced fluorescence in AMs, whereas it was greatly increased in Ms and PMNs (13-fold and 113-fold, respectively). The levels of DCFH-DA-and DHR-induced fluorescence were significantly (p<0.05) increased (four-fold and 110-fold, respectively) by PMA stimulation of PMNs, but not of AMs and Ms. Significant differences (p<0.05) in the levels of DHE-and DCFH-DA-induced fluorescence in small and large AMs were also demonstrated.The results show that the potential to increase the generation of various oxidants upon stimulation was: PMNs> Ms>AMs, suggesting that the total oxidative burden of the lungs is dependent on the type of inflammatory cells present, as well as on their state of activation.

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Increased Number of Alveolar Macrophages Expressing Surface Molecules of the CD11/CD18 Family in Sarcoidosis and Idiopathic Pulmonary Fibrosis Is Related to the Production of Superoxide Anions by These Cells

Cited by 45 publications

References 38 publications

Systemic oxidative stress in patients with pulmonary sarcoidosis

Systemic oxidative stress in patients with pulmonary sarcoidosis

Increased oxidation of extracellular glutathione by bronchoalveolar inflammatory cells in diffuse fibrosing alveolitis

Production of oxidants in alveolar macrophages and blood leukocytes

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